Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study
Abstract Non-syndromic pituitary gigantism can result from AIP mutations or the recently identified Xq26.3 microduplication causing X-linked acrogigantism (XLAG). Within Xq26.3, GPR101 is believed to be the causative gene, and the c.924G > C (p.E308D) variant in this orphan G protein-coupled rece...
Ausführliche Beschreibung
Autor*in: |
Iacovazzo, Donato [verfasserIn] |
---|
Format: |
E-Artikel |
---|---|
Sprache: |
Englisch |
Erschienen: |
2016 |
---|
Schlagwörter: |
---|
Anmerkung: |
© The Author(s). 2016 |
---|
Übergeordnetes Werk: |
Enthalten in: Acta Neuropathologica Communications - London : Biomed Central, 2013, 4(2016), 1 vom: 01. Juni |
---|---|
Übergeordnetes Werk: |
volume:4 ; year:2016 ; number:1 ; day:01 ; month:06 |
Links: |
---|
DOI / URN: |
10.1186/s40478-016-0328-1 |
---|
Katalog-ID: |
SPR036510874 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | SPR036510874 | ||
003 | DE-627 | ||
005 | 20230519195019.0 | ||
007 | cr uuu---uuuuu | ||
008 | 201007s2016 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1186/s40478-016-0328-1 |2 doi | |
035 | |a (DE-627)SPR036510874 | ||
035 | |a (SPR)s40478-016-0328-1-e | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Iacovazzo, Donato |e verfasserin |4 aut | |
245 | 1 | 0 | |a Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study |
264 | 1 | |c 2016 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a Computermedien |b c |2 rdamedia | ||
338 | |a Online-Ressource |b cr |2 rdacarrier | ||
500 | |a © The Author(s). 2016 | ||
520 | |a Abstract Non-syndromic pituitary gigantism can result from AIP mutations or the recently identified Xq26.3 microduplication causing X-linked acrogigantism (XLAG). Within Xq26.3, GPR101 is believed to be the causative gene, and the c.924G > C (p.E308D) variant in this orphan G protein-coupled receptor has been suggested to play a role in the pathogenesis of acromegaly. We studied 153 patients (58 females and 95 males) with pituitary gigantism. AIP mutation-negative cases were screened for GPR101 duplication through copy number variation droplet digital PCR and high-density aCGH. The genetic, clinical and histopathological features of XLAG patients were studied in detail. 395 peripheral blood and 193 pituitary tumor DNA samples from acromegaly patients were tested for GPR101 variants. We identified 12 patients (10 females and 2 males; 7.8 %) with XLAG. In one subject, the duplicated region only contained GPR101, but not the other three genes found to be duplicated in the previously reported patients, defining a new smallest region of overlap of duplications. While females presented with germline mutations, the two male patients harbored the mutation in a mosaic state. Nine patients had pituitary adenomas, while three had hyperplasia. The comparison of the features of XLAG, AIP-positive and GPR101&AIP-negative patients revealed significant differences in sex distribution, age at onset, height, prolactin co-secretion and histological features. The pathological features of XLAG-related adenomas were remarkably similar. These tumors had a sinusoidal and lobular architecture. Sparsely and densely granulated somatotrophs were admixed with lactotrophs; follicle-like structures and calcifications were commonly observed. Patients with sporadic or familial acromegaly did not have an increased prevalence of the c.924G > C (p.E308D) GPR101 variant compared to public databases. In conclusion, XLAG can result from germline or somatic duplication of GPR101. Duplication of GPR101 alone is sufficient for the development of XLAG, implicating it as the causative gene within the Xq26.3 region. The pathological features of XLAG-associated pituitary adenomas are typical and, together with the clinical phenotype, should prompt genetic testing. | ||
650 | 4 | |a XLAG |7 (dpeaa)DE-He213 | |
650 | 4 | |a Gigantism |7 (dpeaa)DE-He213 | |
650 | 4 | |a GPR101 |7 (dpeaa)DE-He213 | |
650 | 4 | |a CNV mutation |7 (dpeaa)DE-He213 | |
650 | 4 | |a Pituitary |7 (dpeaa)DE-He213 | |
700 | 1 | |a Caswell, Richard |4 aut | |
700 | 1 | |a Bunce, Benjamin |4 aut | |
700 | 1 | |a Jose, Sian |4 aut | |
700 | 1 | |a Yuan, Bo |4 aut | |
700 | 1 | |a Hernández-Ramírez, Laura C. |4 aut | |
700 | 1 | |a Kapur, Sonal |4 aut | |
700 | 1 | |a Caimari, Francisca |4 aut | |
700 | 1 | |a Evanson, Jane |4 aut | |
700 | 1 | |a Ferraù, Francesco |4 aut | |
700 | 1 | |a Dang, Mary N. |4 aut | |
700 | 1 | |a Gabrovska, Plamena |4 aut | |
700 | 1 | |a Larkin, Sarah J. |4 aut | |
700 | 1 | |a Ansorge, Olaf |4 aut | |
700 | 1 | |a Rodd, Celia |4 aut | |
700 | 1 | |a Vance, Mary L. |4 aut | |
700 | 1 | |a Ramírez-Renteria, Claudia |4 aut | |
700 | 1 | |a Mercado, Moisés |4 aut | |
700 | 1 | |a Goldstone, Anthony P. |4 aut | |
700 | 1 | |a Buchfelder, Michael |4 aut | |
700 | 1 | |a Burren, Christine P. |4 aut | |
700 | 1 | |a Gurlek, Alper |4 aut | |
700 | 1 | |a Dutta, Pinaki |4 aut | |
700 | 1 | |a Choong, Catherine S. |4 aut | |
700 | 1 | |a Cheetham, Timothy |4 aut | |
700 | 1 | |a Trivellin, Giampaolo |4 aut | |
700 | 1 | |a Stratakis, Constantine A. |4 aut | |
700 | 1 | |a Lopes, Maria-Beatriz |4 aut | |
700 | 1 | |a Grossman, Ashley B. |4 aut | |
700 | 1 | |a Trouillas, Jacqueline |4 aut | |
700 | 1 | |a Lupski, James R. |4 aut | |
700 | 1 | |a Ellard, Sian |4 aut | |
700 | 1 | |a Sampson, Julian R. |4 aut | |
700 | 1 | |a Roncaroli, Federico |4 aut | |
700 | 1 | |a Korbonits, Márta |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Acta Neuropathologica Communications |d London : Biomed Central, 2013 |g 4(2016), 1 vom: 01. Juni |w (DE-627)746066465 |w (DE-600)2715589-4 |x 2051-5960 |7 nnns |
773 | 1 | 8 | |g volume:4 |g year:2016 |g number:1 |g day:01 |g month:06 |
856 | 4 | 0 | |u https://dx.doi.org/10.1186/s40478-016-0328-1 |z kostenfrei |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a SYSFLAG_A | ||
912 | |a GBV_SPRINGER | ||
912 | |a SSG-OLC-PHA | ||
912 | |a GBV_ILN_11 | ||
912 | |a GBV_ILN_20 | ||
912 | |a GBV_ILN_22 | ||
912 | |a GBV_ILN_23 | ||
912 | |a GBV_ILN_24 | ||
912 | |a GBV_ILN_39 | ||
912 | |a GBV_ILN_40 | ||
912 | |a GBV_ILN_60 | ||
912 | |a GBV_ILN_62 | ||
912 | |a GBV_ILN_63 | ||
912 | |a GBV_ILN_65 | ||
912 | |a GBV_ILN_69 | ||
912 | |a GBV_ILN_73 | ||
912 | |a GBV_ILN_74 | ||
912 | |a GBV_ILN_95 | ||
912 | |a GBV_ILN_105 | ||
912 | |a GBV_ILN_110 | ||
912 | |a GBV_ILN_151 | ||
912 | |a GBV_ILN_161 | ||
912 | |a GBV_ILN_170 | ||
912 | |a GBV_ILN_206 | ||
912 | |a GBV_ILN_213 | ||
912 | |a GBV_ILN_230 | ||
912 | |a GBV_ILN_285 | ||
912 | |a GBV_ILN_293 | ||
912 | |a GBV_ILN_602 | ||
912 | |a GBV_ILN_2003 | ||
912 | |a GBV_ILN_2005 | ||
912 | |a GBV_ILN_2009 | ||
912 | |a GBV_ILN_2014 | ||
912 | |a GBV_ILN_2055 | ||
912 | |a GBV_ILN_2111 | ||
912 | |a GBV_ILN_4012 | ||
912 | |a GBV_ILN_4037 | ||
912 | |a GBV_ILN_4112 | ||
912 | |a GBV_ILN_4125 | ||
912 | |a GBV_ILN_4126 | ||
912 | |a GBV_ILN_4249 | ||
912 | |a GBV_ILN_4305 | ||
912 | |a GBV_ILN_4306 | ||
912 | |a GBV_ILN_4307 | ||
912 | |a GBV_ILN_4313 | ||
912 | |a GBV_ILN_4322 | ||
912 | |a GBV_ILN_4323 | ||
912 | |a GBV_ILN_4324 | ||
912 | |a GBV_ILN_4325 | ||
912 | |a GBV_ILN_4338 | ||
912 | |a GBV_ILN_4367 | ||
912 | |a GBV_ILN_4700 | ||
951 | |a AR | ||
952 | |d 4 |j 2016 |e 1 |b 01 |c 06 |
author_variant |
d i di r c rc b b bb s j sj b y by l c h r lch lchr s k sk f c fc j e je f f ff m n d mn mnd p g pg s j l sj sjl o a oa c r cr m l v ml mlv c r r crr m m mm a p g ap apg m b mb c p b cp cpb a g ag p d pd c s c cs csc t c tc g t gt c a s ca cas m b l mbl a b g ab abg j t jt j r l jr jrl s e se j r s jr jrs f r fr m k mk |
---|---|
matchkey_str |
article:20515960:2016----::emieroaigr0dpiainedtxikdcoiatsalncpt |
hierarchy_sort_str |
2016 |
publishDate |
2016 |
allfields |
10.1186/s40478-016-0328-1 doi (DE-627)SPR036510874 (SPR)s40478-016-0328-1-e DE-627 ger DE-627 rakwb eng Iacovazzo, Donato verfasserin aut Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2016 Abstract Non-syndromic pituitary gigantism can result from AIP mutations or the recently identified Xq26.3 microduplication causing X-linked acrogigantism (XLAG). Within Xq26.3, GPR101 is believed to be the causative gene, and the c.924G > C (p.E308D) variant in this orphan G protein-coupled receptor has been suggested to play a role in the pathogenesis of acromegaly. We studied 153 patients (58 females and 95 males) with pituitary gigantism. AIP mutation-negative cases were screened for GPR101 duplication through copy number variation droplet digital PCR and high-density aCGH. The genetic, clinical and histopathological features of XLAG patients were studied in detail. 395 peripheral blood and 193 pituitary tumor DNA samples from acromegaly patients were tested for GPR101 variants. We identified 12 patients (10 females and 2 males; 7.8 %) with XLAG. In one subject, the duplicated region only contained GPR101, but not the other three genes found to be duplicated in the previously reported patients, defining a new smallest region of overlap of duplications. While females presented with germline mutations, the two male patients harbored the mutation in a mosaic state. Nine patients had pituitary adenomas, while three had hyperplasia. The comparison of the features of XLAG, AIP-positive and GPR101&AIP-negative patients revealed significant differences in sex distribution, age at onset, height, prolactin co-secretion and histological features. The pathological features of XLAG-related adenomas were remarkably similar. These tumors had a sinusoidal and lobular architecture. Sparsely and densely granulated somatotrophs were admixed with lactotrophs; follicle-like structures and calcifications were commonly observed. Patients with sporadic or familial acromegaly did not have an increased prevalence of the c.924G > C (p.E308D) GPR101 variant compared to public databases. In conclusion, XLAG can result from germline or somatic duplication of GPR101. Duplication of GPR101 alone is sufficient for the development of XLAG, implicating it as the causative gene within the Xq26.3 region. The pathological features of XLAG-associated pituitary adenomas are typical and, together with the clinical phenotype, should prompt genetic testing. XLAG (dpeaa)DE-He213 Gigantism (dpeaa)DE-He213 GPR101 (dpeaa)DE-He213 CNV mutation (dpeaa)DE-He213 Pituitary (dpeaa)DE-He213 Caswell, Richard aut Bunce, Benjamin aut Jose, Sian aut Yuan, Bo aut Hernández-Ramírez, Laura C. aut Kapur, Sonal aut Caimari, Francisca aut Evanson, Jane aut Ferraù, Francesco aut Dang, Mary N. aut Gabrovska, Plamena aut Larkin, Sarah J. aut Ansorge, Olaf aut Rodd, Celia aut Vance, Mary L. aut Ramírez-Renteria, Claudia aut Mercado, Moisés aut Goldstone, Anthony P. aut Buchfelder, Michael aut Burren, Christine P. aut Gurlek, Alper aut Dutta, Pinaki aut Choong, Catherine S. aut Cheetham, Timothy aut Trivellin, Giampaolo aut Stratakis, Constantine A. aut Lopes, Maria-Beatriz aut Grossman, Ashley B. aut Trouillas, Jacqueline aut Lupski, James R. aut Ellard, Sian aut Sampson, Julian R. aut Roncaroli, Federico aut Korbonits, Márta aut Enthalten in Acta Neuropathologica Communications London : Biomed Central, 2013 4(2016), 1 vom: 01. Juni (DE-627)746066465 (DE-600)2715589-4 2051-5960 nnns volume:4 year:2016 number:1 day:01 month:06 https://dx.doi.org/10.1186/s40478-016-0328-1 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2016 1 01 06 |
spelling |
10.1186/s40478-016-0328-1 doi (DE-627)SPR036510874 (SPR)s40478-016-0328-1-e DE-627 ger DE-627 rakwb eng Iacovazzo, Donato verfasserin aut Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2016 Abstract Non-syndromic pituitary gigantism can result from AIP mutations or the recently identified Xq26.3 microduplication causing X-linked acrogigantism (XLAG). Within Xq26.3, GPR101 is believed to be the causative gene, and the c.924G > C (p.E308D) variant in this orphan G protein-coupled receptor has been suggested to play a role in the pathogenesis of acromegaly. We studied 153 patients (58 females and 95 males) with pituitary gigantism. AIP mutation-negative cases were screened for GPR101 duplication through copy number variation droplet digital PCR and high-density aCGH. The genetic, clinical and histopathological features of XLAG patients were studied in detail. 395 peripheral blood and 193 pituitary tumor DNA samples from acromegaly patients were tested for GPR101 variants. We identified 12 patients (10 females and 2 males; 7.8 %) with XLAG. In one subject, the duplicated region only contained GPR101, but not the other three genes found to be duplicated in the previously reported patients, defining a new smallest region of overlap of duplications. While females presented with germline mutations, the two male patients harbored the mutation in a mosaic state. Nine patients had pituitary adenomas, while three had hyperplasia. The comparison of the features of XLAG, AIP-positive and GPR101&AIP-negative patients revealed significant differences in sex distribution, age at onset, height, prolactin co-secretion and histological features. The pathological features of XLAG-related adenomas were remarkably similar. These tumors had a sinusoidal and lobular architecture. Sparsely and densely granulated somatotrophs were admixed with lactotrophs; follicle-like structures and calcifications were commonly observed. Patients with sporadic or familial acromegaly did not have an increased prevalence of the c.924G > C (p.E308D) GPR101 variant compared to public databases. In conclusion, XLAG can result from germline or somatic duplication of GPR101. Duplication of GPR101 alone is sufficient for the development of XLAG, implicating it as the causative gene within the Xq26.3 region. The pathological features of XLAG-associated pituitary adenomas are typical and, together with the clinical phenotype, should prompt genetic testing. XLAG (dpeaa)DE-He213 Gigantism (dpeaa)DE-He213 GPR101 (dpeaa)DE-He213 CNV mutation (dpeaa)DE-He213 Pituitary (dpeaa)DE-He213 Caswell, Richard aut Bunce, Benjamin aut Jose, Sian aut Yuan, Bo aut Hernández-Ramírez, Laura C. aut Kapur, Sonal aut Caimari, Francisca aut Evanson, Jane aut Ferraù, Francesco aut Dang, Mary N. aut Gabrovska, Plamena aut Larkin, Sarah J. aut Ansorge, Olaf aut Rodd, Celia aut Vance, Mary L. aut Ramírez-Renteria, Claudia aut Mercado, Moisés aut Goldstone, Anthony P. aut Buchfelder, Michael aut Burren, Christine P. aut Gurlek, Alper aut Dutta, Pinaki aut Choong, Catherine S. aut Cheetham, Timothy aut Trivellin, Giampaolo aut Stratakis, Constantine A. aut Lopes, Maria-Beatriz aut Grossman, Ashley B. aut Trouillas, Jacqueline aut Lupski, James R. aut Ellard, Sian aut Sampson, Julian R. aut Roncaroli, Federico aut Korbonits, Márta aut Enthalten in Acta Neuropathologica Communications London : Biomed Central, 2013 4(2016), 1 vom: 01. Juni (DE-627)746066465 (DE-600)2715589-4 2051-5960 nnns volume:4 year:2016 number:1 day:01 month:06 https://dx.doi.org/10.1186/s40478-016-0328-1 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2016 1 01 06 |
allfields_unstemmed |
10.1186/s40478-016-0328-1 doi (DE-627)SPR036510874 (SPR)s40478-016-0328-1-e DE-627 ger DE-627 rakwb eng Iacovazzo, Donato verfasserin aut Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2016 Abstract Non-syndromic pituitary gigantism can result from AIP mutations or the recently identified Xq26.3 microduplication causing X-linked acrogigantism (XLAG). Within Xq26.3, GPR101 is believed to be the causative gene, and the c.924G > C (p.E308D) variant in this orphan G protein-coupled receptor has been suggested to play a role in the pathogenesis of acromegaly. We studied 153 patients (58 females and 95 males) with pituitary gigantism. AIP mutation-negative cases were screened for GPR101 duplication through copy number variation droplet digital PCR and high-density aCGH. The genetic, clinical and histopathological features of XLAG patients were studied in detail. 395 peripheral blood and 193 pituitary tumor DNA samples from acromegaly patients were tested for GPR101 variants. We identified 12 patients (10 females and 2 males; 7.8 %) with XLAG. In one subject, the duplicated region only contained GPR101, but not the other three genes found to be duplicated in the previously reported patients, defining a new smallest region of overlap of duplications. While females presented with germline mutations, the two male patients harbored the mutation in a mosaic state. Nine patients had pituitary adenomas, while three had hyperplasia. The comparison of the features of XLAG, AIP-positive and GPR101&AIP-negative patients revealed significant differences in sex distribution, age at onset, height, prolactin co-secretion and histological features. The pathological features of XLAG-related adenomas were remarkably similar. These tumors had a sinusoidal and lobular architecture. Sparsely and densely granulated somatotrophs were admixed with lactotrophs; follicle-like structures and calcifications were commonly observed. Patients with sporadic or familial acromegaly did not have an increased prevalence of the c.924G > C (p.E308D) GPR101 variant compared to public databases. In conclusion, XLAG can result from germline or somatic duplication of GPR101. Duplication of GPR101 alone is sufficient for the development of XLAG, implicating it as the causative gene within the Xq26.3 region. The pathological features of XLAG-associated pituitary adenomas are typical and, together with the clinical phenotype, should prompt genetic testing. XLAG (dpeaa)DE-He213 Gigantism (dpeaa)DE-He213 GPR101 (dpeaa)DE-He213 CNV mutation (dpeaa)DE-He213 Pituitary (dpeaa)DE-He213 Caswell, Richard aut Bunce, Benjamin aut Jose, Sian aut Yuan, Bo aut Hernández-Ramírez, Laura C. aut Kapur, Sonal aut Caimari, Francisca aut Evanson, Jane aut Ferraù, Francesco aut Dang, Mary N. aut Gabrovska, Plamena aut Larkin, Sarah J. aut Ansorge, Olaf aut Rodd, Celia aut Vance, Mary L. aut Ramírez-Renteria, Claudia aut Mercado, Moisés aut Goldstone, Anthony P. aut Buchfelder, Michael aut Burren, Christine P. aut Gurlek, Alper aut Dutta, Pinaki aut Choong, Catherine S. aut Cheetham, Timothy aut Trivellin, Giampaolo aut Stratakis, Constantine A. aut Lopes, Maria-Beatriz aut Grossman, Ashley B. aut Trouillas, Jacqueline aut Lupski, James R. aut Ellard, Sian aut Sampson, Julian R. aut Roncaroli, Federico aut Korbonits, Márta aut Enthalten in Acta Neuropathologica Communications London : Biomed Central, 2013 4(2016), 1 vom: 01. Juni (DE-627)746066465 (DE-600)2715589-4 2051-5960 nnns volume:4 year:2016 number:1 day:01 month:06 https://dx.doi.org/10.1186/s40478-016-0328-1 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2016 1 01 06 |
allfieldsGer |
10.1186/s40478-016-0328-1 doi (DE-627)SPR036510874 (SPR)s40478-016-0328-1-e DE-627 ger DE-627 rakwb eng Iacovazzo, Donato verfasserin aut Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2016 Abstract Non-syndromic pituitary gigantism can result from AIP mutations or the recently identified Xq26.3 microduplication causing X-linked acrogigantism (XLAG). Within Xq26.3, GPR101 is believed to be the causative gene, and the c.924G > C (p.E308D) variant in this orphan G protein-coupled receptor has been suggested to play a role in the pathogenesis of acromegaly. We studied 153 patients (58 females and 95 males) with pituitary gigantism. AIP mutation-negative cases were screened for GPR101 duplication through copy number variation droplet digital PCR and high-density aCGH. The genetic, clinical and histopathological features of XLAG patients were studied in detail. 395 peripheral blood and 193 pituitary tumor DNA samples from acromegaly patients were tested for GPR101 variants. We identified 12 patients (10 females and 2 males; 7.8 %) with XLAG. In one subject, the duplicated region only contained GPR101, but not the other three genes found to be duplicated in the previously reported patients, defining a new smallest region of overlap of duplications. While females presented with germline mutations, the two male patients harbored the mutation in a mosaic state. Nine patients had pituitary adenomas, while three had hyperplasia. The comparison of the features of XLAG, AIP-positive and GPR101&AIP-negative patients revealed significant differences in sex distribution, age at onset, height, prolactin co-secretion and histological features. The pathological features of XLAG-related adenomas were remarkably similar. These tumors had a sinusoidal and lobular architecture. Sparsely and densely granulated somatotrophs were admixed with lactotrophs; follicle-like structures and calcifications were commonly observed. Patients with sporadic or familial acromegaly did not have an increased prevalence of the c.924G > C (p.E308D) GPR101 variant compared to public databases. In conclusion, XLAG can result from germline or somatic duplication of GPR101. Duplication of GPR101 alone is sufficient for the development of XLAG, implicating it as the causative gene within the Xq26.3 region. The pathological features of XLAG-associated pituitary adenomas are typical and, together with the clinical phenotype, should prompt genetic testing. XLAG (dpeaa)DE-He213 Gigantism (dpeaa)DE-He213 GPR101 (dpeaa)DE-He213 CNV mutation (dpeaa)DE-He213 Pituitary (dpeaa)DE-He213 Caswell, Richard aut Bunce, Benjamin aut Jose, Sian aut Yuan, Bo aut Hernández-Ramírez, Laura C. aut Kapur, Sonal aut Caimari, Francisca aut Evanson, Jane aut Ferraù, Francesco aut Dang, Mary N. aut Gabrovska, Plamena aut Larkin, Sarah J. aut Ansorge, Olaf aut Rodd, Celia aut Vance, Mary L. aut Ramírez-Renteria, Claudia aut Mercado, Moisés aut Goldstone, Anthony P. aut Buchfelder, Michael aut Burren, Christine P. aut Gurlek, Alper aut Dutta, Pinaki aut Choong, Catherine S. aut Cheetham, Timothy aut Trivellin, Giampaolo aut Stratakis, Constantine A. aut Lopes, Maria-Beatriz aut Grossman, Ashley B. aut Trouillas, Jacqueline aut Lupski, James R. aut Ellard, Sian aut Sampson, Julian R. aut Roncaroli, Federico aut Korbonits, Márta aut Enthalten in Acta Neuropathologica Communications London : Biomed Central, 2013 4(2016), 1 vom: 01. Juni (DE-627)746066465 (DE-600)2715589-4 2051-5960 nnns volume:4 year:2016 number:1 day:01 month:06 https://dx.doi.org/10.1186/s40478-016-0328-1 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2016 1 01 06 |
allfieldsSound |
10.1186/s40478-016-0328-1 doi (DE-627)SPR036510874 (SPR)s40478-016-0328-1-e DE-627 ger DE-627 rakwb eng Iacovazzo, Donato verfasserin aut Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2016 Abstract Non-syndromic pituitary gigantism can result from AIP mutations or the recently identified Xq26.3 microduplication causing X-linked acrogigantism (XLAG). Within Xq26.3, GPR101 is believed to be the causative gene, and the c.924G > C (p.E308D) variant in this orphan G protein-coupled receptor has been suggested to play a role in the pathogenesis of acromegaly. We studied 153 patients (58 females and 95 males) with pituitary gigantism. AIP mutation-negative cases were screened for GPR101 duplication through copy number variation droplet digital PCR and high-density aCGH. The genetic, clinical and histopathological features of XLAG patients were studied in detail. 395 peripheral blood and 193 pituitary tumor DNA samples from acromegaly patients were tested for GPR101 variants. We identified 12 patients (10 females and 2 males; 7.8 %) with XLAG. In one subject, the duplicated region only contained GPR101, but not the other three genes found to be duplicated in the previously reported patients, defining a new smallest region of overlap of duplications. While females presented with germline mutations, the two male patients harbored the mutation in a mosaic state. Nine patients had pituitary adenomas, while three had hyperplasia. The comparison of the features of XLAG, AIP-positive and GPR101&AIP-negative patients revealed significant differences in sex distribution, age at onset, height, prolactin co-secretion and histological features. The pathological features of XLAG-related adenomas were remarkably similar. These tumors had a sinusoidal and lobular architecture. Sparsely and densely granulated somatotrophs were admixed with lactotrophs; follicle-like structures and calcifications were commonly observed. Patients with sporadic or familial acromegaly did not have an increased prevalence of the c.924G > C (p.E308D) GPR101 variant compared to public databases. In conclusion, XLAG can result from germline or somatic duplication of GPR101. Duplication of GPR101 alone is sufficient for the development of XLAG, implicating it as the causative gene within the Xq26.3 region. The pathological features of XLAG-associated pituitary adenomas are typical and, together with the clinical phenotype, should prompt genetic testing. XLAG (dpeaa)DE-He213 Gigantism (dpeaa)DE-He213 GPR101 (dpeaa)DE-He213 CNV mutation (dpeaa)DE-He213 Pituitary (dpeaa)DE-He213 Caswell, Richard aut Bunce, Benjamin aut Jose, Sian aut Yuan, Bo aut Hernández-Ramírez, Laura C. aut Kapur, Sonal aut Caimari, Francisca aut Evanson, Jane aut Ferraù, Francesco aut Dang, Mary N. aut Gabrovska, Plamena aut Larkin, Sarah J. aut Ansorge, Olaf aut Rodd, Celia aut Vance, Mary L. aut Ramírez-Renteria, Claudia aut Mercado, Moisés aut Goldstone, Anthony P. aut Buchfelder, Michael aut Burren, Christine P. aut Gurlek, Alper aut Dutta, Pinaki aut Choong, Catherine S. aut Cheetham, Timothy aut Trivellin, Giampaolo aut Stratakis, Constantine A. aut Lopes, Maria-Beatriz aut Grossman, Ashley B. aut Trouillas, Jacqueline aut Lupski, James R. aut Ellard, Sian aut Sampson, Julian R. aut Roncaroli, Federico aut Korbonits, Márta aut Enthalten in Acta Neuropathologica Communications London : Biomed Central, 2013 4(2016), 1 vom: 01. Juni (DE-627)746066465 (DE-600)2715589-4 2051-5960 nnns volume:4 year:2016 number:1 day:01 month:06 https://dx.doi.org/10.1186/s40478-016-0328-1 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 4 2016 1 01 06 |
language |
English |
source |
Enthalten in Acta Neuropathologica Communications 4(2016), 1 vom: 01. Juni volume:4 year:2016 number:1 day:01 month:06 |
sourceStr |
Enthalten in Acta Neuropathologica Communications 4(2016), 1 vom: 01. Juni volume:4 year:2016 number:1 day:01 month:06 |
format_phy_str_mv |
Article |
institution |
findex.gbv.de |
topic_facet |
XLAG Gigantism GPR101 CNV mutation Pituitary |
isfreeaccess_bool |
true |
container_title |
Acta Neuropathologica Communications |
authorswithroles_txt_mv |
Iacovazzo, Donato @@aut@@ Caswell, Richard @@aut@@ Bunce, Benjamin @@aut@@ Jose, Sian @@aut@@ Yuan, Bo @@aut@@ Hernández-Ramírez, Laura C. @@aut@@ Kapur, Sonal @@aut@@ Caimari, Francisca @@aut@@ Evanson, Jane @@aut@@ Ferraù, Francesco @@aut@@ Dang, Mary N. @@aut@@ Gabrovska, Plamena @@aut@@ Larkin, Sarah J. @@aut@@ Ansorge, Olaf @@aut@@ Rodd, Celia @@aut@@ Vance, Mary L. @@aut@@ Ramírez-Renteria, Claudia @@aut@@ Mercado, Moisés @@aut@@ Goldstone, Anthony P. @@aut@@ Buchfelder, Michael @@aut@@ Burren, Christine P. @@aut@@ Gurlek, Alper @@aut@@ Dutta, Pinaki @@aut@@ Choong, Catherine S. @@aut@@ Cheetham, Timothy @@aut@@ Trivellin, Giampaolo @@aut@@ Stratakis, Constantine A. @@aut@@ Lopes, Maria-Beatriz @@aut@@ Grossman, Ashley B. @@aut@@ Trouillas, Jacqueline @@aut@@ Lupski, James R. @@aut@@ Ellard, Sian @@aut@@ Sampson, Julian R. @@aut@@ Roncaroli, Federico @@aut@@ Korbonits, Márta @@aut@@ |
publishDateDaySort_date |
2016-06-01T00:00:00Z |
hierarchy_top_id |
746066465 |
id |
SPR036510874 |
language_de |
englisch |
fullrecord |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR036510874</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519195019.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201007s2016 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s40478-016-0328-1</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR036510874</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s40478-016-0328-1-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Iacovazzo, Donato</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2016</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© The Author(s). 2016</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Non-syndromic pituitary gigantism can result from AIP mutations or the recently identified Xq26.3 microduplication causing X-linked acrogigantism (XLAG). Within Xq26.3, GPR101 is believed to be the causative gene, and the c.924G > C (p.E308D) variant in this orphan G protein-coupled receptor has been suggested to play a role in the pathogenesis of acromegaly. We studied 153 patients (58 females and 95 males) with pituitary gigantism. AIP mutation-negative cases were screened for GPR101 duplication through copy number variation droplet digital PCR and high-density aCGH. The genetic, clinical and histopathological features of XLAG patients were studied in detail. 395 peripheral blood and 193 pituitary tumor DNA samples from acromegaly patients were tested for GPR101 variants. We identified 12 patients (10 females and 2 males; 7.8 %) with XLAG. In one subject, the duplicated region only contained GPR101, but not the other three genes found to be duplicated in the previously reported patients, defining a new smallest region of overlap of duplications. While females presented with germline mutations, the two male patients harbored the mutation in a mosaic state. Nine patients had pituitary adenomas, while three had hyperplasia. The comparison of the features of XLAG, AIP-positive and GPR101&AIP-negative patients revealed significant differences in sex distribution, age at onset, height, prolactin co-secretion and histological features. The pathological features of XLAG-related adenomas were remarkably similar. These tumors had a sinusoidal and lobular architecture. Sparsely and densely granulated somatotrophs were admixed with lactotrophs; follicle-like structures and calcifications were commonly observed. Patients with sporadic or familial acromegaly did not have an increased prevalence of the c.924G > C (p.E308D) GPR101 variant compared to public databases. In conclusion, XLAG can result from germline or somatic duplication of GPR101. Duplication of GPR101 alone is sufficient for the development of XLAG, implicating it as the causative gene within the Xq26.3 region. The pathological features of XLAG-associated pituitary adenomas are typical and, together with the clinical phenotype, should prompt genetic testing.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">XLAG</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Gigantism</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">GPR101</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">CNV mutation</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Pituitary</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Caswell, Richard</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Bunce, Benjamin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Jose, Sian</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Yuan, Bo</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Hernández-Ramírez, Laura C.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Kapur, Sonal</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Caimari, Francisca</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Evanson, Jane</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Ferraù, Francesco</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Dang, Mary N.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Gabrovska, Plamena</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Larkin, Sarah J.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Ansorge, Olaf</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Rodd, Celia</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Vance, Mary L.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Ramírez-Renteria, Claudia</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Mercado, Moisés</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Goldstone, Anthony P.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Buchfelder, Michael</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Burren, Christine P.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Gurlek, Alper</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Dutta, Pinaki</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Choong, Catherine S.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Cheetham, Timothy</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Trivellin, Giampaolo</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Stratakis, Constantine A.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Lopes, Maria-Beatriz</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Grossman, Ashley B.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Trouillas, Jacqueline</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Lupski, James R.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Ellard, Sian</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Sampson, Julian R.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Roncaroli, Federico</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Korbonits, Márta</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Acta Neuropathologica Communications</subfield><subfield code="d">London : Biomed Central, 2013</subfield><subfield code="g">4(2016), 1 vom: 01. Juni</subfield><subfield code="w">(DE-627)746066465</subfield><subfield code="w">(DE-600)2715589-4</subfield><subfield code="x">2051-5960</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:4</subfield><subfield code="g">year:2016</subfield><subfield code="g">number:1</subfield><subfield code="g">day:01</subfield><subfield code="g">month:06</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://dx.doi.org/10.1186/s40478-016-0328-1</subfield><subfield code="z">kostenfrei</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_SPRINGER</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_11</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2003</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2005</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2009</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2055</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2111</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">4</subfield><subfield code="j">2016</subfield><subfield code="e">1</subfield><subfield code="b">01</subfield><subfield code="c">06</subfield></datafield></record></collection>
|
author |
Iacovazzo, Donato |
spellingShingle |
Iacovazzo, Donato misc XLAG misc Gigantism misc GPR101 misc CNV mutation misc Pituitary Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study |
authorStr |
Iacovazzo, Donato |
ppnlink_with_tag_str_mv |
@@773@@(DE-627)746066465 |
format |
electronic Article |
delete_txt_mv |
keep |
author_role |
aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut |
collection |
springer |
remote_str |
true |
illustrated |
Not Illustrated |
issn |
2051-5960 |
topic_title |
Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study XLAG (dpeaa)DE-He213 Gigantism (dpeaa)DE-He213 GPR101 (dpeaa)DE-He213 CNV mutation (dpeaa)DE-He213 Pituitary (dpeaa)DE-He213 |
topic |
misc XLAG misc Gigantism misc GPR101 misc CNV mutation misc Pituitary |
topic_unstemmed |
misc XLAG misc Gigantism misc GPR101 misc CNV mutation misc Pituitary |
topic_browse |
misc XLAG misc Gigantism misc GPR101 misc CNV mutation misc Pituitary |
format_facet |
Elektronische Aufsätze Aufsätze Elektronische Ressource |
format_main_str_mv |
Text Zeitschrift/Artikel |
carriertype_str_mv |
cr |
hierarchy_parent_title |
Acta Neuropathologica Communications |
hierarchy_parent_id |
746066465 |
hierarchy_top_title |
Acta Neuropathologica Communications |
isfreeaccess_txt |
true |
familylinks_str_mv |
(DE-627)746066465 (DE-600)2715589-4 |
title |
Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study |
ctrlnum |
(DE-627)SPR036510874 (SPR)s40478-016-0328-1-e |
title_full |
Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study |
author_sort |
Iacovazzo, Donato |
journal |
Acta Neuropathologica Communications |
journalStr |
Acta Neuropathologica Communications |
lang_code |
eng |
isOA_bool |
true |
recordtype |
marc |
publishDateSort |
2016 |
contenttype_str_mv |
txt |
author_browse |
Iacovazzo, Donato Caswell, Richard Bunce, Benjamin Jose, Sian Yuan, Bo Hernández-Ramírez, Laura C. Kapur, Sonal Caimari, Francisca Evanson, Jane Ferraù, Francesco Dang, Mary N. Gabrovska, Plamena Larkin, Sarah J. Ansorge, Olaf Rodd, Celia Vance, Mary L. Ramírez-Renteria, Claudia Mercado, Moisés Goldstone, Anthony P. Buchfelder, Michael Burren, Christine P. Gurlek, Alper Dutta, Pinaki Choong, Catherine S. Cheetham, Timothy Trivellin, Giampaolo Stratakis, Constantine A. Lopes, Maria-Beatriz Grossman, Ashley B. Trouillas, Jacqueline Lupski, James R. Ellard, Sian Sampson, Julian R. Roncaroli, Federico Korbonits, Márta |
container_volume |
4 |
format_se |
Elektronische Aufsätze |
author-letter |
Iacovazzo, Donato |
doi_str_mv |
10.1186/s40478-016-0328-1 |
title_sort |
germline or somatic gpr101 duplication leads to x-linked acrogigantism: a clinico-pathological and genetic study |
title_auth |
Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study |
abstract |
Abstract Non-syndromic pituitary gigantism can result from AIP mutations or the recently identified Xq26.3 microduplication causing X-linked acrogigantism (XLAG). Within Xq26.3, GPR101 is believed to be the causative gene, and the c.924G > C (p.E308D) variant in this orphan G protein-coupled receptor has been suggested to play a role in the pathogenesis of acromegaly. We studied 153 patients (58 females and 95 males) with pituitary gigantism. AIP mutation-negative cases were screened for GPR101 duplication through copy number variation droplet digital PCR and high-density aCGH. The genetic, clinical and histopathological features of XLAG patients were studied in detail. 395 peripheral blood and 193 pituitary tumor DNA samples from acromegaly patients were tested for GPR101 variants. We identified 12 patients (10 females and 2 males; 7.8 %) with XLAG. In one subject, the duplicated region only contained GPR101, but not the other three genes found to be duplicated in the previously reported patients, defining a new smallest region of overlap of duplications. While females presented with germline mutations, the two male patients harbored the mutation in a mosaic state. Nine patients had pituitary adenomas, while three had hyperplasia. The comparison of the features of XLAG, AIP-positive and GPR101&AIP-negative patients revealed significant differences in sex distribution, age at onset, height, prolactin co-secretion and histological features. The pathological features of XLAG-related adenomas were remarkably similar. These tumors had a sinusoidal and lobular architecture. Sparsely and densely granulated somatotrophs were admixed with lactotrophs; follicle-like structures and calcifications were commonly observed. Patients with sporadic or familial acromegaly did not have an increased prevalence of the c.924G > C (p.E308D) GPR101 variant compared to public databases. In conclusion, XLAG can result from germline or somatic duplication of GPR101. Duplication of GPR101 alone is sufficient for the development of XLAG, implicating it as the causative gene within the Xq26.3 region. The pathological features of XLAG-associated pituitary adenomas are typical and, together with the clinical phenotype, should prompt genetic testing. © The Author(s). 2016 |
abstractGer |
Abstract Non-syndromic pituitary gigantism can result from AIP mutations or the recently identified Xq26.3 microduplication causing X-linked acrogigantism (XLAG). Within Xq26.3, GPR101 is believed to be the causative gene, and the c.924G > C (p.E308D) variant in this orphan G protein-coupled receptor has been suggested to play a role in the pathogenesis of acromegaly. We studied 153 patients (58 females and 95 males) with pituitary gigantism. AIP mutation-negative cases were screened for GPR101 duplication through copy number variation droplet digital PCR and high-density aCGH. The genetic, clinical and histopathological features of XLAG patients were studied in detail. 395 peripheral blood and 193 pituitary tumor DNA samples from acromegaly patients were tested for GPR101 variants. We identified 12 patients (10 females and 2 males; 7.8 %) with XLAG. In one subject, the duplicated region only contained GPR101, but not the other three genes found to be duplicated in the previously reported patients, defining a new smallest region of overlap of duplications. While females presented with germline mutations, the two male patients harbored the mutation in a mosaic state. Nine patients had pituitary adenomas, while three had hyperplasia. The comparison of the features of XLAG, AIP-positive and GPR101&AIP-negative patients revealed significant differences in sex distribution, age at onset, height, prolactin co-secretion and histological features. The pathological features of XLAG-related adenomas were remarkably similar. These tumors had a sinusoidal and lobular architecture. Sparsely and densely granulated somatotrophs were admixed with lactotrophs; follicle-like structures and calcifications were commonly observed. Patients with sporadic or familial acromegaly did not have an increased prevalence of the c.924G > C (p.E308D) GPR101 variant compared to public databases. In conclusion, XLAG can result from germline or somatic duplication of GPR101. Duplication of GPR101 alone is sufficient for the development of XLAG, implicating it as the causative gene within the Xq26.3 region. The pathological features of XLAG-associated pituitary adenomas are typical and, together with the clinical phenotype, should prompt genetic testing. © The Author(s). 2016 |
abstract_unstemmed |
Abstract Non-syndromic pituitary gigantism can result from AIP mutations or the recently identified Xq26.3 microduplication causing X-linked acrogigantism (XLAG). Within Xq26.3, GPR101 is believed to be the causative gene, and the c.924G > C (p.E308D) variant in this orphan G protein-coupled receptor has been suggested to play a role in the pathogenesis of acromegaly. We studied 153 patients (58 females and 95 males) with pituitary gigantism. AIP mutation-negative cases were screened for GPR101 duplication through copy number variation droplet digital PCR and high-density aCGH. The genetic, clinical and histopathological features of XLAG patients were studied in detail. 395 peripheral blood and 193 pituitary tumor DNA samples from acromegaly patients were tested for GPR101 variants. We identified 12 patients (10 females and 2 males; 7.8 %) with XLAG. In one subject, the duplicated region only contained GPR101, but not the other three genes found to be duplicated in the previously reported patients, defining a new smallest region of overlap of duplications. While females presented with germline mutations, the two male patients harbored the mutation in a mosaic state. Nine patients had pituitary adenomas, while three had hyperplasia. The comparison of the features of XLAG, AIP-positive and GPR101&AIP-negative patients revealed significant differences in sex distribution, age at onset, height, prolactin co-secretion and histological features. The pathological features of XLAG-related adenomas were remarkably similar. These tumors had a sinusoidal and lobular architecture. Sparsely and densely granulated somatotrophs were admixed with lactotrophs; follicle-like structures and calcifications were commonly observed. Patients with sporadic or familial acromegaly did not have an increased prevalence of the c.924G > C (p.E308D) GPR101 variant compared to public databases. In conclusion, XLAG can result from germline or somatic duplication of GPR101. Duplication of GPR101 alone is sufficient for the development of XLAG, implicating it as the causative gene within the Xq26.3 region. The pathological features of XLAG-associated pituitary adenomas are typical and, together with the clinical phenotype, should prompt genetic testing. © The Author(s). 2016 |
collection_details |
GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 |
container_issue |
1 |
title_short |
Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study |
url |
https://dx.doi.org/10.1186/s40478-016-0328-1 |
remote_bool |
true |
author2 |
Caswell, Richard Bunce, Benjamin Jose, Sian Yuan, Bo Hernández-Ramírez, Laura C. Kapur, Sonal Caimari, Francisca Evanson, Jane Ferraù, Francesco Dang, Mary N. Gabrovska, Plamena Larkin, Sarah J. Ansorge, Olaf Rodd, Celia Vance, Mary L. Ramírez-Renteria, Claudia Mercado, Moisés Goldstone, Anthony P. Buchfelder, Michael Burren, Christine P. Gurlek, Alper Dutta, Pinaki Choong, Catherine S. Cheetham, Timothy Trivellin, Giampaolo Stratakis, Constantine A. Lopes, Maria-Beatriz Grossman, Ashley B. Trouillas, Jacqueline Lupski, James R. Ellard, Sian Sampson, Julian R. Roncaroli, Federico Korbonits, Márta |
author2Str |
Caswell, Richard Bunce, Benjamin Jose, Sian Yuan, Bo Hernández-Ramírez, Laura C. Kapur, Sonal Caimari, Francisca Evanson, Jane Ferraù, Francesco Dang, Mary N. Gabrovska, Plamena Larkin, Sarah J. Ansorge, Olaf Rodd, Celia Vance, Mary L. Ramírez-Renteria, Claudia Mercado, Moisés Goldstone, Anthony P. Buchfelder, Michael Burren, Christine P. Gurlek, Alper Dutta, Pinaki Choong, Catherine S. Cheetham, Timothy Trivellin, Giampaolo Stratakis, Constantine A. Lopes, Maria-Beatriz Grossman, Ashley B. Trouillas, Jacqueline Lupski, James R. Ellard, Sian Sampson, Julian R. Roncaroli, Federico Korbonits, Márta |
ppnlink |
746066465 |
mediatype_str_mv |
c |
isOA_txt |
true |
hochschulschrift_bool |
false |
doi_str |
10.1186/s40478-016-0328-1 |
up_date |
2024-07-03T18:04:02.863Z |
_version_ |
1803582012518301696 |
fullrecord_marcxml |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR036510874</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519195019.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201007s2016 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s40478-016-0328-1</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR036510874</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s40478-016-0328-1-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Iacovazzo, Donato</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2016</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© The Author(s). 2016</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Non-syndromic pituitary gigantism can result from AIP mutations or the recently identified Xq26.3 microduplication causing X-linked acrogigantism (XLAG). Within Xq26.3, GPR101 is believed to be the causative gene, and the c.924G > C (p.E308D) variant in this orphan G protein-coupled receptor has been suggested to play a role in the pathogenesis of acromegaly. We studied 153 patients (58 females and 95 males) with pituitary gigantism. AIP mutation-negative cases were screened for GPR101 duplication through copy number variation droplet digital PCR and high-density aCGH. The genetic, clinical and histopathological features of XLAG patients were studied in detail. 395 peripheral blood and 193 pituitary tumor DNA samples from acromegaly patients were tested for GPR101 variants. We identified 12 patients (10 females and 2 males; 7.8 %) with XLAG. In one subject, the duplicated region only contained GPR101, but not the other three genes found to be duplicated in the previously reported patients, defining a new smallest region of overlap of duplications. While females presented with germline mutations, the two male patients harbored the mutation in a mosaic state. Nine patients had pituitary adenomas, while three had hyperplasia. The comparison of the features of XLAG, AIP-positive and GPR101&AIP-negative patients revealed significant differences in sex distribution, age at onset, height, prolactin co-secretion and histological features. The pathological features of XLAG-related adenomas were remarkably similar. These tumors had a sinusoidal and lobular architecture. Sparsely and densely granulated somatotrophs were admixed with lactotrophs; follicle-like structures and calcifications were commonly observed. Patients with sporadic or familial acromegaly did not have an increased prevalence of the c.924G > C (p.E308D) GPR101 variant compared to public databases. In conclusion, XLAG can result from germline or somatic duplication of GPR101. Duplication of GPR101 alone is sufficient for the development of XLAG, implicating it as the causative gene within the Xq26.3 region. The pathological features of XLAG-associated pituitary adenomas are typical and, together with the clinical phenotype, should prompt genetic testing.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">XLAG</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Gigantism</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">GPR101</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">CNV mutation</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Pituitary</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Caswell, Richard</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Bunce, Benjamin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Jose, Sian</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Yuan, Bo</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Hernández-Ramírez, Laura C.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Kapur, Sonal</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Caimari, Francisca</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Evanson, Jane</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Ferraù, Francesco</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Dang, Mary N.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Gabrovska, Plamena</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Larkin, Sarah J.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Ansorge, Olaf</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Rodd, Celia</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Vance, Mary L.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Ramírez-Renteria, Claudia</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Mercado, Moisés</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Goldstone, Anthony P.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Buchfelder, Michael</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Burren, Christine P.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Gurlek, Alper</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Dutta, Pinaki</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Choong, Catherine S.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Cheetham, Timothy</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Trivellin, Giampaolo</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Stratakis, Constantine A.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Lopes, Maria-Beatriz</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Grossman, Ashley B.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Trouillas, Jacqueline</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Lupski, James R.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Ellard, Sian</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Sampson, Julian R.</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Roncaroli, Federico</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Korbonits, Márta</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Acta Neuropathologica Communications</subfield><subfield code="d">London : Biomed Central, 2013</subfield><subfield code="g">4(2016), 1 vom: 01. Juni</subfield><subfield code="w">(DE-627)746066465</subfield><subfield code="w">(DE-600)2715589-4</subfield><subfield code="x">2051-5960</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:4</subfield><subfield code="g">year:2016</subfield><subfield code="g">number:1</subfield><subfield code="g">day:01</subfield><subfield code="g">month:06</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://dx.doi.org/10.1186/s40478-016-0328-1</subfield><subfield code="z">kostenfrei</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_SPRINGER</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_11</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2003</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2005</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2009</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2055</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2111</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">4</subfield><subfield code="j">2016</subfield><subfield code="e">1</subfield><subfield code="b">01</subfield><subfield code="c">06</subfield></datafield></record></collection>
|
score |
7.4010954 |