Identification of a novel mutation in the KITLG gene in a Chinese family with familial progressive hyper- and hypopigmentation

Abstract Background Familial progressive hyper- and hypopigmentation (FPHH, MIM 145250) is a rare hereditary skin disorder that is predominantly characterized by progressive, diffuse, partly blotchy hyperpigmented lesions intermingled with scattered hypopigmented spots, lentigines and sometimes Cafe-au-lait spots (CALs). Heterozygous mutations of the KIT ligand (KITLG, MIM 184745) gene are responsible for FPHH. To date, only eight KITLG mutations have been reported to be associated with FPHH, and no clear genotype–phenotype correlations have been established. This study aimed to identify the causative mutations in the KITLG gene in two Chinese FPHH patients. Methods Direct sequencing of the coding regions of KITLG was performed. Pathogenicity prediction was performed using bioinformatics tools, including SIFT, Polyphen2, and SWISS-MODEL, and the results were further evaluated according to the 2015 American College of Medical Genetics and Genomics (ACMG) guidelines. Results The novel mutation c.104A < T (p.Asn35Ile) and the recurrent mutation c.101C < T (p.Thr34Ile) in KITLG were identified. As shown using SIFT and Polyphen-2 software, both mutations identified in this study were predicted to be detrimental variations. Three-dimensional protein structure modeling indicated that the mutant KITLG proteins might affect the affinity of KITLG for its receptor, c-KIT. According to the 2015 ACMG guidelines, the novel mutation c.104A < T was ‘likely pathogenic’. Conclusions To date, most of the identified KITLG mutations have been clustered within the conserved VTNNV motif (amino acids 33–37) in exon 2. The known mutations are only involved in 33 V, 34 T, 36 N, and 37 V but not 35 N. We have now identified a novel mutation in KITLG, c.104A < T, that was first reported in FPHH within the conserved 35 N motif. These results strengthen our understanding of FPHH and expand the mutational spectrum of the KITLG gene. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Jianbo Wang [verfasserIn] Weisheng Li [verfasserIn] Naihui Zhou [verfasserIn] Jingliu Liu [verfasserIn] Shoumin Zhang [verfasserIn] Xueli Li [verfasserIn] Zhenlu Li [verfasserIn] Ziliang Yang [verfasserIn] Miao Sun [verfasserIn] Min Li [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	Familial progressive hyper- and hypopigmentation KITLG gene Mutation VTNNV motif

Übergeordnetes Werk:	In: BMC Medical Genomics - BMC, 2008, 14(2021), 1, Seite 7
Übergeordnetes Werk:	volume:14 ; year:2021 ; number:1 ; pages:7

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s12920-020-00851-5

Katalog-ID:	DOAJ077950860

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520			\|a Abstract Background Familial progressive hyper- and hypopigmentation (FPHH, MIM 145250) is a rare hereditary skin disorder that is predominantly characterized by progressive, diffuse, partly blotchy hyperpigmented lesions intermingled with scattered hypopigmented spots, lentigines and sometimes Cafe-au-lait spots (CALs). Heterozygous mutations of the KIT ligand (KITLG, MIM 184745) gene are responsible for FPHH. To date, only eight KITLG mutations have been reported to be associated with FPHH, and no clear genotype–phenotype correlations have been established. This study aimed to identify the causative mutations in the KITLG gene in two Chinese FPHH patients. Methods Direct sequencing of the coding regions of KITLG was performed. Pathogenicity prediction was performed using bioinformatics tools, including SIFT, Polyphen2, and SWISS-MODEL, and the results were further evaluated according to the 2015 American College of Medical Genetics and Genomics (ACMG) guidelines. Results The novel mutation c.104A < T (p.Asn35Ile) and the recurrent mutation c.101C < T (p.Thr34Ile) in KITLG were identified. As shown using SIFT and Polyphen-2 software, both mutations identified in this study were predicted to be detrimental variations. Three-dimensional protein structure modeling indicated that the mutant KITLG proteins might affect the affinity of KITLG for its receptor, c-KIT. According to the 2015 ACMG guidelines, the novel mutation c.104A < T was ‘likely pathogenic’. Conclusions To date, most of the identified KITLG mutations have been clustered within the conserved VTNNV motif (amino acids 33–37) in exon 2. The known mutations are only involved in 33 V, 34 T, 36 N, and 37 V but not 35 N. We have now identified a novel mutation in KITLG, c.104A < T, that was first reported in FPHH within the conserved 35 N motif. These results strengthen our understanding of FPHH and expand the mutational spectrum of the KITLG gene.
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allfields	10.1186/s12920-020-00851-5 doi (DE-627)DOAJ077950860 (DE-599)DOAJ949068c66e4c431d996c487725be2e1b DE-627 ger DE-627 rakwb eng RC31-1245 QH426-470 Jianbo Wang verfasserin aut Identification of a novel mutation in the KITLG gene in a Chinese family with familial progressive hyper- and hypopigmentation 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Familial progressive hyper- and hypopigmentation (FPHH, MIM 145250) is a rare hereditary skin disorder that is predominantly characterized by progressive, diffuse, partly blotchy hyperpigmented lesions intermingled with scattered hypopigmented spots, lentigines and sometimes Cafe-au-lait spots (CALs). Heterozygous mutations of the KIT ligand (KITLG, MIM 184745) gene are responsible for FPHH. To date, only eight KITLG mutations have been reported to be associated with FPHH, and no clear genotype–phenotype correlations have been established. This study aimed to identify the causative mutations in the KITLG gene in two Chinese FPHH patients. Methods Direct sequencing of the coding regions of KITLG was performed. Pathogenicity prediction was performed using bioinformatics tools, including SIFT, Polyphen2, and SWISS-MODEL, and the results were further evaluated according to the 2015 American College of Medical Genetics and Genomics (ACMG) guidelines. Results The novel mutation c.104A < T (p.Asn35Ile) and the recurrent mutation c.101C < T (p.Thr34Ile) in KITLG were identified. As shown using SIFT and Polyphen-2 software, both mutations identified in this study were predicted to be detrimental variations. Three-dimensional protein structure modeling indicated that the mutant KITLG proteins might affect the affinity of KITLG for its receptor, c-KIT. According to the 2015 ACMG guidelines, the novel mutation c.104A < T was ‘likely pathogenic’. Conclusions To date, most of the identified KITLG mutations have been clustered within the conserved VTNNV motif (amino acids 33–37) in exon 2. The known mutations are only involved in 33 V, 34 T, 36 N, and 37 V but not 35 N. We have now identified a novel mutation in KITLG, c.104A < T, that was first reported in FPHH within the conserved 35 N motif. These results strengthen our understanding of FPHH and expand the mutational spectrum of the KITLG gene. Familial progressive hyper- and hypopigmentation KITLG gene Mutation VTNNV motif Internal medicine Genetics Weisheng Li verfasserin aut Naihui Zhou verfasserin aut Jingliu Liu verfasserin aut Shoumin Zhang verfasserin aut Xueli Li verfasserin aut Zhenlu Li verfasserin aut Ziliang Yang verfasserin aut Miao Sun verfasserin aut Min Li verfasserin aut In BMC Medical Genomics BMC, 2008 14(2021), 1, Seite 7 (DE-627)559080824 (DE-600)2411865-5 17558794 nnns volume:14 year:2021 number:1 pages:7 https://doi.org/10.1186/s12920-020-00851-5 kostenfrei https://doaj.org/article/949068c66e4c431d996c487725be2e1b kostenfrei https://doi.org/10.1186/s12920-020-00851-5 kostenfrei https://doaj.org/toc/1755-8794 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_2011 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 14 2021 1 7
spelling	10.1186/s12920-020-00851-5 doi (DE-627)DOAJ077950860 (DE-599)DOAJ949068c66e4c431d996c487725be2e1b DE-627 ger DE-627 rakwb eng RC31-1245 QH426-470 Jianbo Wang verfasserin aut Identification of a novel mutation in the KITLG gene in a Chinese family with familial progressive hyper- and hypopigmentation 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Familial progressive hyper- and hypopigmentation (FPHH, MIM 145250) is a rare hereditary skin disorder that is predominantly characterized by progressive, diffuse, partly blotchy hyperpigmented lesions intermingled with scattered hypopigmented spots, lentigines and sometimes Cafe-au-lait spots (CALs). Heterozygous mutations of the KIT ligand (KITLG, MIM 184745) gene are responsible for FPHH. To date, only eight KITLG mutations have been reported to be associated with FPHH, and no clear genotype–phenotype correlations have been established. This study aimed to identify the causative mutations in the KITLG gene in two Chinese FPHH patients. Methods Direct sequencing of the coding regions of KITLG was performed. Pathogenicity prediction was performed using bioinformatics tools, including SIFT, Polyphen2, and SWISS-MODEL, and the results were further evaluated according to the 2015 American College of Medical Genetics and Genomics (ACMG) guidelines. Results The novel mutation c.104A < T (p.Asn35Ile) and the recurrent mutation c.101C < T (p.Thr34Ile) in KITLG were identified. As shown using SIFT and Polyphen-2 software, both mutations identified in this study were predicted to be detrimental variations. Three-dimensional protein structure modeling indicated that the mutant KITLG proteins might affect the affinity of KITLG for its receptor, c-KIT. According to the 2015 ACMG guidelines, the novel mutation c.104A < T was ‘likely pathogenic’. Conclusions To date, most of the identified KITLG mutations have been clustered within the conserved VTNNV motif (amino acids 33–37) in exon 2. The known mutations are only involved in 33 V, 34 T, 36 N, and 37 V but not 35 N. We have now identified a novel mutation in KITLG, c.104A < T, that was first reported in FPHH within the conserved 35 N motif. These results strengthen our understanding of FPHH and expand the mutational spectrum of the KITLG gene. Familial progressive hyper- and hypopigmentation KITLG gene Mutation VTNNV motif Internal medicine Genetics Weisheng Li verfasserin aut Naihui Zhou verfasserin aut Jingliu Liu verfasserin aut Shoumin Zhang verfasserin aut Xueli Li verfasserin aut Zhenlu Li verfasserin aut Ziliang Yang verfasserin aut Miao Sun verfasserin aut Min Li verfasserin aut In BMC Medical Genomics BMC, 2008 14(2021), 1, Seite 7 (DE-627)559080824 (DE-600)2411865-5 17558794 nnns volume:14 year:2021 number:1 pages:7 https://doi.org/10.1186/s12920-020-00851-5 kostenfrei https://doaj.org/article/949068c66e4c431d996c487725be2e1b kostenfrei https://doi.org/10.1186/s12920-020-00851-5 kostenfrei https://doaj.org/toc/1755-8794 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_2011 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 14 2021 1 7
allfields_unstemmed	10.1186/s12920-020-00851-5 doi (DE-627)DOAJ077950860 (DE-599)DOAJ949068c66e4c431d996c487725be2e1b DE-627 ger DE-627 rakwb eng RC31-1245 QH426-470 Jianbo Wang verfasserin aut Identification of a novel mutation in the KITLG gene in a Chinese family with familial progressive hyper- and hypopigmentation 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Familial progressive hyper- and hypopigmentation (FPHH, MIM 145250) is a rare hereditary skin disorder that is predominantly characterized by progressive, diffuse, partly blotchy hyperpigmented lesions intermingled with scattered hypopigmented spots, lentigines and sometimes Cafe-au-lait spots (CALs). Heterozygous mutations of the KIT ligand (KITLG, MIM 184745) gene are responsible for FPHH. To date, only eight KITLG mutations have been reported to be associated with FPHH, and no clear genotype–phenotype correlations have been established. This study aimed to identify the causative mutations in the KITLG gene in two Chinese FPHH patients. Methods Direct sequencing of the coding regions of KITLG was performed. Pathogenicity prediction was performed using bioinformatics tools, including SIFT, Polyphen2, and SWISS-MODEL, and the results were further evaluated according to the 2015 American College of Medical Genetics and Genomics (ACMG) guidelines. Results The novel mutation c.104A < T (p.Asn35Ile) and the recurrent mutation c.101C < T (p.Thr34Ile) in KITLG were identified. As shown using SIFT and Polyphen-2 software, both mutations identified in this study were predicted to be detrimental variations. Three-dimensional protein structure modeling indicated that the mutant KITLG proteins might affect the affinity of KITLG for its receptor, c-KIT. According to the 2015 ACMG guidelines, the novel mutation c.104A < T was ‘likely pathogenic’. Conclusions To date, most of the identified KITLG mutations have been clustered within the conserved VTNNV motif (amino acids 33–37) in exon 2. The known mutations are only involved in 33 V, 34 T, 36 N, and 37 V but not 35 N. We have now identified a novel mutation in KITLG, c.104A < T, that was first reported in FPHH within the conserved 35 N motif. These results strengthen our understanding of FPHH and expand the mutational spectrum of the KITLG gene. Familial progressive hyper- and hypopigmentation KITLG gene Mutation VTNNV motif Internal medicine Genetics Weisheng Li verfasserin aut Naihui Zhou verfasserin aut Jingliu Liu verfasserin aut Shoumin Zhang verfasserin aut Xueli Li verfasserin aut Zhenlu Li verfasserin aut Ziliang Yang verfasserin aut Miao Sun verfasserin aut Min Li verfasserin aut In BMC Medical Genomics BMC, 2008 14(2021), 1, Seite 7 (DE-627)559080824 (DE-600)2411865-5 17558794 nnns volume:14 year:2021 number:1 pages:7 https://doi.org/10.1186/s12920-020-00851-5 kostenfrei https://doaj.org/article/949068c66e4c431d996c487725be2e1b kostenfrei https://doi.org/10.1186/s12920-020-00851-5 kostenfrei https://doaj.org/toc/1755-8794 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_2011 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 14 2021 1 7
allfieldsGer	10.1186/s12920-020-00851-5 doi (DE-627)DOAJ077950860 (DE-599)DOAJ949068c66e4c431d996c487725be2e1b DE-627 ger DE-627 rakwb eng RC31-1245 QH426-470 Jianbo Wang verfasserin aut Identification of a novel mutation in the KITLG gene in a Chinese family with familial progressive hyper- and hypopigmentation 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Familial progressive hyper- and hypopigmentation (FPHH, MIM 145250) is a rare hereditary skin disorder that is predominantly characterized by progressive, diffuse, partly blotchy hyperpigmented lesions intermingled with scattered hypopigmented spots, lentigines and sometimes Cafe-au-lait spots (CALs). Heterozygous mutations of the KIT ligand (KITLG, MIM 184745) gene are responsible for FPHH. To date, only eight KITLG mutations have been reported to be associated with FPHH, and no clear genotype–phenotype correlations have been established. This study aimed to identify the causative mutations in the KITLG gene in two Chinese FPHH patients. Methods Direct sequencing of the coding regions of KITLG was performed. Pathogenicity prediction was performed using bioinformatics tools, including SIFT, Polyphen2, and SWISS-MODEL, and the results were further evaluated according to the 2015 American College of Medical Genetics and Genomics (ACMG) guidelines. Results The novel mutation c.104A < T (p.Asn35Ile) and the recurrent mutation c.101C < T (p.Thr34Ile) in KITLG were identified. As shown using SIFT and Polyphen-2 software, both mutations identified in this study were predicted to be detrimental variations. Three-dimensional protein structure modeling indicated that the mutant KITLG proteins might affect the affinity of KITLG for its receptor, c-KIT. According to the 2015 ACMG guidelines, the novel mutation c.104A < T was ‘likely pathogenic’. Conclusions To date, most of the identified KITLG mutations have been clustered within the conserved VTNNV motif (amino acids 33–37) in exon 2. The known mutations are only involved in 33 V, 34 T, 36 N, and 37 V but not 35 N. We have now identified a novel mutation in KITLG, c.104A < T, that was first reported in FPHH within the conserved 35 N motif. These results strengthen our understanding of FPHH and expand the mutational spectrum of the KITLG gene. Familial progressive hyper- and hypopigmentation KITLG gene Mutation VTNNV motif Internal medicine Genetics Weisheng Li verfasserin aut Naihui Zhou verfasserin aut Jingliu Liu verfasserin aut Shoumin Zhang verfasserin aut Xueli Li verfasserin aut Zhenlu Li verfasserin aut Ziliang Yang verfasserin aut Miao Sun verfasserin aut Min Li verfasserin aut In BMC Medical Genomics BMC, 2008 14(2021), 1, Seite 7 (DE-627)559080824 (DE-600)2411865-5 17558794 nnns volume:14 year:2021 number:1 pages:7 https://doi.org/10.1186/s12920-020-00851-5 kostenfrei https://doaj.org/article/949068c66e4c431d996c487725be2e1b kostenfrei https://doi.org/10.1186/s12920-020-00851-5 kostenfrei https://doaj.org/toc/1755-8794 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_2011 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 14 2021 1 7
allfieldsSound	10.1186/s12920-020-00851-5 doi (DE-627)DOAJ077950860 (DE-599)DOAJ949068c66e4c431d996c487725be2e1b DE-627 ger DE-627 rakwb eng RC31-1245 QH426-470 Jianbo Wang verfasserin aut Identification of a novel mutation in the KITLG gene in a Chinese family with familial progressive hyper- and hypopigmentation 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Familial progressive hyper- and hypopigmentation (FPHH, MIM 145250) is a rare hereditary skin disorder that is predominantly characterized by progressive, diffuse, partly blotchy hyperpigmented lesions intermingled with scattered hypopigmented spots, lentigines and sometimes Cafe-au-lait spots (CALs). Heterozygous mutations of the KIT ligand (KITLG, MIM 184745) gene are responsible for FPHH. To date, only eight KITLG mutations have been reported to be associated with FPHH, and no clear genotype–phenotype correlations have been established. This study aimed to identify the causative mutations in the KITLG gene in two Chinese FPHH patients. Methods Direct sequencing of the coding regions of KITLG was performed. Pathogenicity prediction was performed using bioinformatics tools, including SIFT, Polyphen2, and SWISS-MODEL, and the results were further evaluated according to the 2015 American College of Medical Genetics and Genomics (ACMG) guidelines. Results The novel mutation c.104A < T (p.Asn35Ile) and the recurrent mutation c.101C < T (p.Thr34Ile) in KITLG were identified. As shown using SIFT and Polyphen-2 software, both mutations identified in this study were predicted to be detrimental variations. Three-dimensional protein structure modeling indicated that the mutant KITLG proteins might affect the affinity of KITLG for its receptor, c-KIT. According to the 2015 ACMG guidelines, the novel mutation c.104A < T was ‘likely pathogenic’. Conclusions To date, most of the identified KITLG mutations have been clustered within the conserved VTNNV motif (amino acids 33–37) in exon 2. The known mutations are only involved in 33 V, 34 T, 36 N, and 37 V but not 35 N. We have now identified a novel mutation in KITLG, c.104A < T, that was first reported in FPHH within the conserved 35 N motif. These results strengthen our understanding of FPHH and expand the mutational spectrum of the KITLG gene. Familial progressive hyper- and hypopigmentation KITLG gene Mutation VTNNV motif Internal medicine Genetics Weisheng Li verfasserin aut Naihui Zhou verfasserin aut Jingliu Liu verfasserin aut Shoumin Zhang verfasserin aut Xueli Li verfasserin aut Zhenlu Li verfasserin aut Ziliang Yang verfasserin aut Miao Sun verfasserin aut Min Li verfasserin aut In BMC Medical Genomics BMC, 2008 14(2021), 1, Seite 7 (DE-627)559080824 (DE-600)2411865-5 17558794 nnns volume:14 year:2021 number:1 pages:7 https://doi.org/10.1186/s12920-020-00851-5 kostenfrei https://doaj.org/article/949068c66e4c431d996c487725be2e1b kostenfrei https://doi.org/10.1186/s12920-020-00851-5 kostenfrei https://doaj.org/toc/1755-8794 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 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_2011 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 14 2021 1 7
language	English
source	In BMC Medical Genomics 14(2021), 1, Seite 7 volume:14 year:2021 number:1 pages:7
sourceStr	In BMC Medical Genomics 14(2021), 1, Seite 7 volume:14 year:2021 number:1 pages:7
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Familial progressive hyper- and hypopigmentation KITLG gene Mutation VTNNV motif Internal medicine Genetics
isfreeaccess_bool	true
container_title	BMC Medical Genomics
authorswithroles_txt_mv	Jianbo Wang @@aut@@ Weisheng Li @@aut@@ Naihui Zhou @@aut@@ Jingliu Liu @@aut@@ Shoumin Zhang @@aut@@ Xueli Li @@aut@@ Zhenlu Li @@aut@@ Ziliang Yang @@aut@@ Miao Sun @@aut@@ Min Li @@aut@@
publishDateDaySort_date	2021-01-01T00:00:00Z
hierarchy_top_id	559080824
id	DOAJ077950860
language_de	englisch
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Heterozygous mutations of the KIT ligand (KITLG, MIM 184745) gene are responsible for FPHH. To date, only eight KITLG mutations have been reported to be associated with FPHH, and no clear genotype–phenotype correlations have been established. This study aimed to identify the causative mutations in the KITLG gene in two Chinese FPHH patients. Methods Direct sequencing of the coding regions of KITLG was performed. Pathogenicity prediction was performed using bioinformatics tools, including SIFT, Polyphen2, and SWISS-MODEL, and the results were further evaluated according to the 2015 American College of Medical Genetics and Genomics (ACMG) guidelines. Results The novel mutation c.104A < T (p.Asn35Ile) and the recurrent mutation c.101C < T (p.Thr34Ile) in KITLG were identified. As shown using SIFT and Polyphen-2 software, both mutations identified in this study were predicted to be detrimental variations. Three-dimensional protein structure modeling indicated that the mutant KITLG proteins might affect the affinity of KITLG for its receptor, c-KIT. According to the 2015 ACMG guidelines, the novel mutation c.104A < T was ‘likely pathogenic’. Conclusions To date, most of the identified KITLG mutations have been clustered within the conserved VTNNV motif (amino acids 33–37) in exon 2. The known mutations are only involved in 33 V, 34 T, 36 N, and 37 V but not 35 N. We have now identified a novel mutation in KITLG, c.104A < T, that was first reported in FPHH within the conserved 35 N motif. 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callnumber-first	R - Medicine
author	Jianbo Wang
spellingShingle	Jianbo Wang misc RC31-1245 misc QH426-470 misc Familial progressive hyper- and hypopigmentation misc KITLG gene misc Mutation misc VTNNV motif misc Internal medicine misc Genetics Identification of a novel mutation in the KITLG gene in a Chinese family with familial progressive hyper- and hypopigmentation
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topic_title	RC31-1245 QH426-470 Identification of a novel mutation in the KITLG gene in a Chinese family with familial progressive hyper- and hypopigmentation Familial progressive hyper- and hypopigmentation KITLG gene Mutation VTNNV motif
topic	misc RC31-1245 misc QH426-470 misc Familial progressive hyper- and hypopigmentation misc KITLG gene misc Mutation misc VTNNV motif misc Internal medicine misc Genetics
topic_unstemmed	misc RC31-1245 misc QH426-470 misc Familial progressive hyper- and hypopigmentation misc KITLG gene misc Mutation misc VTNNV motif misc Internal medicine misc Genetics
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title	Identification of a novel mutation in the KITLG gene in a Chinese family with familial progressive hyper- and hypopigmentation
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title_full	Identification of a novel mutation in the KITLG gene in a Chinese family with familial progressive hyper- and hypopigmentation
author_sort	Jianbo Wang
journal	BMC Medical Genomics
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author_browse	Jianbo Wang Weisheng Li Naihui Zhou Jingliu Liu Shoumin Zhang Xueli Li Zhenlu Li Ziliang Yang Miao Sun Min Li
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title_sort	identification of a novel mutation in the kitlg gene in a chinese family with familial progressive hyper- and hypopigmentation
callnumber	RC31-1245
title_auth	Identification of a novel mutation in the KITLG gene in a Chinese family with familial progressive hyper- and hypopigmentation
abstract	Abstract Background Familial progressive hyper- and hypopigmentation (FPHH, MIM 145250) is a rare hereditary skin disorder that is predominantly characterized by progressive, diffuse, partly blotchy hyperpigmented lesions intermingled with scattered hypopigmented spots, lentigines and sometimes Cafe-au-lait spots (CALs). Heterozygous mutations of the KIT ligand (KITLG, MIM 184745) gene are responsible for FPHH. To date, only eight KITLG mutations have been reported to be associated with FPHH, and no clear genotype–phenotype correlations have been established. This study aimed to identify the causative mutations in the KITLG gene in two Chinese FPHH patients. Methods Direct sequencing of the coding regions of KITLG was performed. Pathogenicity prediction was performed using bioinformatics tools, including SIFT, Polyphen2, and SWISS-MODEL, and the results were further evaluated according to the 2015 American College of Medical Genetics and Genomics (ACMG) guidelines. Results The novel mutation c.104A < T (p.Asn35Ile) and the recurrent mutation c.101C < T (p.Thr34Ile) in KITLG were identified. As shown using SIFT and Polyphen-2 software, both mutations identified in this study were predicted to be detrimental variations. Three-dimensional protein structure modeling indicated that the mutant KITLG proteins might affect the affinity of KITLG for its receptor, c-KIT. According to the 2015 ACMG guidelines, the novel mutation c.104A < T was ‘likely pathogenic’. Conclusions To date, most of the identified KITLG mutations have been clustered within the conserved VTNNV motif (amino acids 33–37) in exon 2. The known mutations are only involved in 33 V, 34 T, 36 N, and 37 V but not 35 N. We have now identified a novel mutation in KITLG, c.104A < T, that was first reported in FPHH within the conserved 35 N motif. These results strengthen our understanding of FPHH and expand the mutational spectrum of the KITLG gene.
abstractGer	Abstract Background Familial progressive hyper- and hypopigmentation (FPHH, MIM 145250) is a rare hereditary skin disorder that is predominantly characterized by progressive, diffuse, partly blotchy hyperpigmented lesions intermingled with scattered hypopigmented spots, lentigines and sometimes Cafe-au-lait spots (CALs). Heterozygous mutations of the KIT ligand (KITLG, MIM 184745) gene are responsible for FPHH. To date, only eight KITLG mutations have been reported to be associated with FPHH, and no clear genotype–phenotype correlations have been established. This study aimed to identify the causative mutations in the KITLG gene in two Chinese FPHH patients. Methods Direct sequencing of the coding regions of KITLG was performed. Pathogenicity prediction was performed using bioinformatics tools, including SIFT, Polyphen2, and SWISS-MODEL, and the results were further evaluated according to the 2015 American College of Medical Genetics and Genomics (ACMG) guidelines. Results The novel mutation c.104A < T (p.Asn35Ile) and the recurrent mutation c.101C < T (p.Thr34Ile) in KITLG were identified. As shown using SIFT and Polyphen-2 software, both mutations identified in this study were predicted to be detrimental variations. Three-dimensional protein structure modeling indicated that the mutant KITLG proteins might affect the affinity of KITLG for its receptor, c-KIT. According to the 2015 ACMG guidelines, the novel mutation c.104A < T was ‘likely pathogenic’. Conclusions To date, most of the identified KITLG mutations have been clustered within the conserved VTNNV motif (amino acids 33–37) in exon 2. The known mutations are only involved in 33 V, 34 T, 36 N, and 37 V but not 35 N. We have now identified a novel mutation in KITLG, c.104A < T, that was first reported in FPHH within the conserved 35 N motif. These results strengthen our understanding of FPHH and expand the mutational spectrum of the KITLG gene.
abstract_unstemmed	Abstract Background Familial progressive hyper- and hypopigmentation (FPHH, MIM 145250) is a rare hereditary skin disorder that is predominantly characterized by progressive, diffuse, partly blotchy hyperpigmented lesions intermingled with scattered hypopigmented spots, lentigines and sometimes Cafe-au-lait spots (CALs). Heterozygous mutations of the KIT ligand (KITLG, MIM 184745) gene are responsible for FPHH. To date, only eight KITLG mutations have been reported to be associated with FPHH, and no clear genotype–phenotype correlations have been established. This study aimed to identify the causative mutations in the KITLG gene in two Chinese FPHH patients. Methods Direct sequencing of the coding regions of KITLG was performed. Pathogenicity prediction was performed using bioinformatics tools, including SIFT, Polyphen2, and SWISS-MODEL, and the results were further evaluated according to the 2015 American College of Medical Genetics and Genomics (ACMG) guidelines. Results The novel mutation c.104A < T (p.Asn35Ile) and the recurrent mutation c.101C < T (p.Thr34Ile) in KITLG were identified. As shown using SIFT and Polyphen-2 software, both mutations identified in this study were predicted to be detrimental variations. Three-dimensional protein structure modeling indicated that the mutant KITLG proteins might affect the affinity of KITLG for its receptor, c-KIT. According to the 2015 ACMG guidelines, the novel mutation c.104A < T was ‘likely pathogenic’. Conclusions To date, most of the identified KITLG mutations have been clustered within the conserved VTNNV motif (amino acids 33–37) in exon 2. The known mutations are only involved in 33 V, 34 T, 36 N, and 37 V but not 35 N. We have now identified a novel mutation in KITLG, c.104A < T, that was first reported in FPHH within the conserved 35 N motif. These results strengthen our understanding of FPHH and expand the mutational spectrum of the KITLG gene.
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title_short	Identification of a novel mutation in the KITLG gene in a Chinese family with familial progressive hyper- and hypopigmentation
url	https://doi.org/10.1186/s12920-020-00851-5 https://doaj.org/article/949068c66e4c431d996c487725be2e1b https://doaj.org/toc/1755-8794
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Identification of a novel mutation in the KITLG gene in a Chinese family with familial progressive hyper- and hypopigmentation

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