Novel frameshift variants expand the map of the genetic defects in IRF2BP2

BackgroundAt present, the knowledge about disease-causing mutations in IRF2BP2 is very limited because only a few patients affected by this condition have been reported. As previous studies have described, the haploinsufficiency of this interferon transcriptional corepressors leads to the development of CVID. Very recently, a more accurate phenotype produced by truncating variants in this gene has been defined, manifesting CVID with gastrointestinal inflammatory symptoms and autoimmune manifestations.MethodsWe analyzed 5 index cases with suspected primary immunodeficiency by high throughput sequencing. They were submitted for a genetic test with a panel of genes associated with immune system diseases, including IRF2BP2. The screening of SNVs, indels and CNVs fulfilling the criteria with very low allelic frequency and high protein impact, revealed five novel variants in IRF2BP2. In addition, we isolated both wild-type and mutated allele of the cDNA from one of the families.ResultsIn this study, we report five novel loss-of-function (LoF) mutations in IRF2BP2 that likely cause primary immunodeficiency, with CVID as more frequent phenotype, variable expression of inflammatory gastrointestinal features, and one patient with predisposition of viral infection. All identified variants were frameshift changes, and one of them was a large deletion located on chromosome 1q42, which includes the whole sequence of IRF2BP2, among other genes. Both de novo and dominant modes of inheritance were observed in the families here presented, as well as incomplete penetrance.ConclusionsWe describe novel variants in a delimited low-complex region, which may be considered a hotspot in IRF2BP2. Moreover, this is the first time that a large CNV in IRF2BP2 has been reported to cause CVID. The distinct mechanisms than LoF in IRF2BP2 could cause different phenotype compared with the mainly described. Further investigations are necessary to comprehend the regulatory mechanisms of IRF2BP2, which could be under variable expression of the disease. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	José María García-Aznar [verfasserIn] Emilia Maneiro Pampín [verfasserIn] Maite García Ramos [verfasserIn] María José Acuña Pérez [verfasserIn] Nerea Paz Gandiaga [verfasserIn] Laura Minguell Domingo [verfasserIn] Olga Calavia [verfasserIn] Pere Soler-Palacin [verfasserIn] Roger Colobran [verfasserIn] Erika M. Novoa Bolívar [verfasserIn] Javier Gonzalo Ocejo Vinyals [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	IRF2BP2 CVID colitis primary immunodeficiency loss-of-function mutations

Übergeordnetes Werk:	In: Frontiers in Immunology - Frontiers Media S.A., 2011, 14(2023)
Übergeordnetes Werk:	volume:14 ; year:2023

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fimmu.2023.1279171

Katalog-ID:	DOAJ09185783X

Internformat


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100	0		\|a José María García-Aznar \|e verfasserin \|4 aut
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520			\|a BackgroundAt present, the knowledge about disease-causing mutations in IRF2BP2 is very limited because only a few patients affected by this condition have been reported. As previous studies have described, the haploinsufficiency of this interferon transcriptional corepressors leads to the development of CVID. Very recently, a more accurate phenotype produced by truncating variants in this gene has been defined, manifesting CVID with gastrointestinal inflammatory symptoms and autoimmune manifestations.MethodsWe analyzed 5 index cases with suspected primary immunodeficiency by high throughput sequencing. They were submitted for a genetic test with a panel of genes associated with immune system diseases, including IRF2BP2. The screening of SNVs, indels and CNVs fulfilling the criteria with very low allelic frequency and high protein impact, revealed five novel variants in IRF2BP2. In addition, we isolated both wild-type and mutated allele of the cDNA from one of the families.ResultsIn this study, we report five novel loss-of-function (LoF) mutations in IRF2BP2 that likely cause primary immunodeficiency, with CVID as more frequent phenotype, variable expression of inflammatory gastrointestinal features, and one patient with predisposition of viral infection. All identified variants were frameshift changes, and one of them was a large deletion located on chromosome 1q42, which includes the whole sequence of IRF2BP2, among other genes. Both de novo and dominant modes of inheritance were observed in the families here presented, as well as incomplete penetrance.ConclusionsWe describe novel variants in a delimited low-complex region, which may be considered a hotspot in IRF2BP2. Moreover, this is the first time that a large CNV in IRF2BP2 has been reported to cause CVID. The distinct mechanisms than LoF in IRF2BP2 could cause different phenotype compared with the mainly described. Further investigations are necessary to comprehend the regulatory mechanisms of IRF2BP2, which could be under variable expression of the disease.
650		4	\|a IRF2BP2
650		4	\|a CVID
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653		0	\|a Immunologic diseases. Allergy
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allfields	10.3389/fimmu.2023.1279171 doi (DE-627)DOAJ09185783X (DE-599)DOAJde4d55f278164823b4e8b63927542c96 DE-627 ger DE-627 rakwb eng RC581-607 José María García-Aznar verfasserin aut Novel frameshift variants expand the map of the genetic defects in IRF2BP2 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundAt present, the knowledge about disease-causing mutations in IRF2BP2 is very limited because only a few patients affected by this condition have been reported. As previous studies have described, the haploinsufficiency of this interferon transcriptional corepressors leads to the development of CVID. Very recently, a more accurate phenotype produced by truncating variants in this gene has been defined, manifesting CVID with gastrointestinal inflammatory symptoms and autoimmune manifestations.MethodsWe analyzed 5 index cases with suspected primary immunodeficiency by high throughput sequencing. They were submitted for a genetic test with a panel of genes associated with immune system diseases, including IRF2BP2. The screening of SNVs, indels and CNVs fulfilling the criteria with very low allelic frequency and high protein impact, revealed five novel variants in IRF2BP2. In addition, we isolated both wild-type and mutated allele of the cDNA from one of the families.ResultsIn this study, we report five novel loss-of-function (LoF) mutations in IRF2BP2 that likely cause primary immunodeficiency, with CVID as more frequent phenotype, variable expression of inflammatory gastrointestinal features, and one patient with predisposition of viral infection. All identified variants were frameshift changes, and one of them was a large deletion located on chromosome 1q42, which includes the whole sequence of IRF2BP2, among other genes. Both de novo and dominant modes of inheritance were observed in the families here presented, as well as incomplete penetrance.ConclusionsWe describe novel variants in a delimited low-complex region, which may be considered a hotspot in IRF2BP2. Moreover, this is the first time that a large CNV in IRF2BP2 has been reported to cause CVID. The distinct mechanisms than LoF in IRF2BP2 could cause different phenotype compared with the mainly described. Further investigations are necessary to comprehend the regulatory mechanisms of IRF2BP2, which could be under variable expression of the disease. IRF2BP2 CVID colitis primary immunodeficiency loss-of-function mutations Immunologic diseases. Allergy Emilia Maneiro Pampín verfasserin aut Maite García Ramos verfasserin aut María José Acuña Pérez verfasserin aut Nerea Paz Gandiaga verfasserin aut Laura Minguell Domingo verfasserin aut Olga Calavia verfasserin aut Pere Soler-Palacin verfasserin aut Pere Soler-Palacin verfasserin aut Roger Colobran verfasserin aut Roger Colobran verfasserin aut Roger Colobran verfasserin aut Roger Colobran verfasserin aut Erika M. Novoa Bolívar verfasserin aut Javier Gonzalo Ocejo Vinyals verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 14(2023) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:14 year:2023 https://doi.org/10.3389/fimmu.2023.1279171 kostenfrei https://doaj.org/article/de4d55f278164823b4e8b63927542c96 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2023.1279171/full kostenfrei https://doaj.org/toc/1664-3224 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_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_2014 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 2023
spelling	10.3389/fimmu.2023.1279171 doi (DE-627)DOAJ09185783X (DE-599)DOAJde4d55f278164823b4e8b63927542c96 DE-627 ger DE-627 rakwb eng RC581-607 José María García-Aznar verfasserin aut Novel frameshift variants expand the map of the genetic defects in IRF2BP2 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundAt present, the knowledge about disease-causing mutations in IRF2BP2 is very limited because only a few patients affected by this condition have been reported. As previous studies have described, the haploinsufficiency of this interferon transcriptional corepressors leads to the development of CVID. Very recently, a more accurate phenotype produced by truncating variants in this gene has been defined, manifesting CVID with gastrointestinal inflammatory symptoms and autoimmune manifestations.MethodsWe analyzed 5 index cases with suspected primary immunodeficiency by high throughput sequencing. They were submitted for a genetic test with a panel of genes associated with immune system diseases, including IRF2BP2. The screening of SNVs, indels and CNVs fulfilling the criteria with very low allelic frequency and high protein impact, revealed five novel variants in IRF2BP2. In addition, we isolated both wild-type and mutated allele of the cDNA from one of the families.ResultsIn this study, we report five novel loss-of-function (LoF) mutations in IRF2BP2 that likely cause primary immunodeficiency, with CVID as more frequent phenotype, variable expression of inflammatory gastrointestinal features, and one patient with predisposition of viral infection. All identified variants were frameshift changes, and one of them was a large deletion located on chromosome 1q42, which includes the whole sequence of IRF2BP2, among other genes. Both de novo and dominant modes of inheritance were observed in the families here presented, as well as incomplete penetrance.ConclusionsWe describe novel variants in a delimited low-complex region, which may be considered a hotspot in IRF2BP2. Moreover, this is the first time that a large CNV in IRF2BP2 has been reported to cause CVID. The distinct mechanisms than LoF in IRF2BP2 could cause different phenotype compared with the mainly described. Further investigations are necessary to comprehend the regulatory mechanisms of IRF2BP2, which could be under variable expression of the disease. IRF2BP2 CVID colitis primary immunodeficiency loss-of-function mutations Immunologic diseases. Allergy Emilia Maneiro Pampín verfasserin aut Maite García Ramos verfasserin aut María José Acuña Pérez verfasserin aut Nerea Paz Gandiaga verfasserin aut Laura Minguell Domingo verfasserin aut Olga Calavia verfasserin aut Pere Soler-Palacin verfasserin aut Pere Soler-Palacin verfasserin aut Roger Colobran verfasserin aut Roger Colobran verfasserin aut Roger Colobran verfasserin aut Roger Colobran verfasserin aut Erika M. Novoa Bolívar verfasserin aut Javier Gonzalo Ocejo Vinyals verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 14(2023) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:14 year:2023 https://doi.org/10.3389/fimmu.2023.1279171 kostenfrei https://doaj.org/article/de4d55f278164823b4e8b63927542c96 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2023.1279171/full kostenfrei https://doaj.org/toc/1664-3224 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_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_2014 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 2023
allfields_unstemmed	10.3389/fimmu.2023.1279171 doi (DE-627)DOAJ09185783X (DE-599)DOAJde4d55f278164823b4e8b63927542c96 DE-627 ger DE-627 rakwb eng RC581-607 José María García-Aznar verfasserin aut Novel frameshift variants expand the map of the genetic defects in IRF2BP2 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundAt present, the knowledge about disease-causing mutations in IRF2BP2 is very limited because only a few patients affected by this condition have been reported. As previous studies have described, the haploinsufficiency of this interferon transcriptional corepressors leads to the development of CVID. Very recently, a more accurate phenotype produced by truncating variants in this gene has been defined, manifesting CVID with gastrointestinal inflammatory symptoms and autoimmune manifestations.MethodsWe analyzed 5 index cases with suspected primary immunodeficiency by high throughput sequencing. They were submitted for a genetic test with a panel of genes associated with immune system diseases, including IRF2BP2. The screening of SNVs, indels and CNVs fulfilling the criteria with very low allelic frequency and high protein impact, revealed five novel variants in IRF2BP2. In addition, we isolated both wild-type and mutated allele of the cDNA from one of the families.ResultsIn this study, we report five novel loss-of-function (LoF) mutations in IRF2BP2 that likely cause primary immunodeficiency, with CVID as more frequent phenotype, variable expression of inflammatory gastrointestinal features, and one patient with predisposition of viral infection. All identified variants were frameshift changes, and one of them was a large deletion located on chromosome 1q42, which includes the whole sequence of IRF2BP2, among other genes. Both de novo and dominant modes of inheritance were observed in the families here presented, as well as incomplete penetrance.ConclusionsWe describe novel variants in a delimited low-complex region, which may be considered a hotspot in IRF2BP2. Moreover, this is the first time that a large CNV in IRF2BP2 has been reported to cause CVID. The distinct mechanisms than LoF in IRF2BP2 could cause different phenotype compared with the mainly described. Further investigations are necessary to comprehend the regulatory mechanisms of IRF2BP2, which could be under variable expression of the disease. IRF2BP2 CVID colitis primary immunodeficiency loss-of-function mutations Immunologic diseases. Allergy Emilia Maneiro Pampín verfasserin aut Maite García Ramos verfasserin aut María José Acuña Pérez verfasserin aut Nerea Paz Gandiaga verfasserin aut Laura Minguell Domingo verfasserin aut Olga Calavia verfasserin aut Pere Soler-Palacin verfasserin aut Pere Soler-Palacin verfasserin aut Roger Colobran verfasserin aut Roger Colobran verfasserin aut Roger Colobran verfasserin aut Roger Colobran verfasserin aut Erika M. Novoa Bolívar verfasserin aut Javier Gonzalo Ocejo Vinyals verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 14(2023) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:14 year:2023 https://doi.org/10.3389/fimmu.2023.1279171 kostenfrei https://doaj.org/article/de4d55f278164823b4e8b63927542c96 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2023.1279171/full kostenfrei https://doaj.org/toc/1664-3224 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_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_2014 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 2023
allfieldsGer	10.3389/fimmu.2023.1279171 doi (DE-627)DOAJ09185783X (DE-599)DOAJde4d55f278164823b4e8b63927542c96 DE-627 ger DE-627 rakwb eng RC581-607 José María García-Aznar verfasserin aut Novel frameshift variants expand the map of the genetic defects in IRF2BP2 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundAt present, the knowledge about disease-causing mutations in IRF2BP2 is very limited because only a few patients affected by this condition have been reported. As previous studies have described, the haploinsufficiency of this interferon transcriptional corepressors leads to the development of CVID. Very recently, a more accurate phenotype produced by truncating variants in this gene has been defined, manifesting CVID with gastrointestinal inflammatory symptoms and autoimmune manifestations.MethodsWe analyzed 5 index cases with suspected primary immunodeficiency by high throughput sequencing. They were submitted for a genetic test with a panel of genes associated with immune system diseases, including IRF2BP2. The screening of SNVs, indels and CNVs fulfilling the criteria with very low allelic frequency and high protein impact, revealed five novel variants in IRF2BP2. In addition, we isolated both wild-type and mutated allele of the cDNA from one of the families.ResultsIn this study, we report five novel loss-of-function (LoF) mutations in IRF2BP2 that likely cause primary immunodeficiency, with CVID as more frequent phenotype, variable expression of inflammatory gastrointestinal features, and one patient with predisposition of viral infection. All identified variants were frameshift changes, and one of them was a large deletion located on chromosome 1q42, which includes the whole sequence of IRF2BP2, among other genes. Both de novo and dominant modes of inheritance were observed in the families here presented, as well as incomplete penetrance.ConclusionsWe describe novel variants in a delimited low-complex region, which may be considered a hotspot in IRF2BP2. Moreover, this is the first time that a large CNV in IRF2BP2 has been reported to cause CVID. The distinct mechanisms than LoF in IRF2BP2 could cause different phenotype compared with the mainly described. Further investigations are necessary to comprehend the regulatory mechanisms of IRF2BP2, which could be under variable expression of the disease. IRF2BP2 CVID colitis primary immunodeficiency loss-of-function mutations Immunologic diseases. Allergy Emilia Maneiro Pampín verfasserin aut Maite García Ramos verfasserin aut María José Acuña Pérez verfasserin aut Nerea Paz Gandiaga verfasserin aut Laura Minguell Domingo verfasserin aut Olga Calavia verfasserin aut Pere Soler-Palacin verfasserin aut Pere Soler-Palacin verfasserin aut Roger Colobran verfasserin aut Roger Colobran verfasserin aut Roger Colobran verfasserin aut Roger Colobran verfasserin aut Erika M. Novoa Bolívar verfasserin aut Javier Gonzalo Ocejo Vinyals verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 14(2023) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:14 year:2023 https://doi.org/10.3389/fimmu.2023.1279171 kostenfrei https://doaj.org/article/de4d55f278164823b4e8b63927542c96 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2023.1279171/full kostenfrei https://doaj.org/toc/1664-3224 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_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_2014 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 2023
allfieldsSound	10.3389/fimmu.2023.1279171 doi (DE-627)DOAJ09185783X (DE-599)DOAJde4d55f278164823b4e8b63927542c96 DE-627 ger DE-627 rakwb eng RC581-607 José María García-Aznar verfasserin aut Novel frameshift variants expand the map of the genetic defects in IRF2BP2 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundAt present, the knowledge about disease-causing mutations in IRF2BP2 is very limited because only a few patients affected by this condition have been reported. As previous studies have described, the haploinsufficiency of this interferon transcriptional corepressors leads to the development of CVID. Very recently, a more accurate phenotype produced by truncating variants in this gene has been defined, manifesting CVID with gastrointestinal inflammatory symptoms and autoimmune manifestations.MethodsWe analyzed 5 index cases with suspected primary immunodeficiency by high throughput sequencing. They were submitted for a genetic test with a panel of genes associated with immune system diseases, including IRF2BP2. The screening of SNVs, indels and CNVs fulfilling the criteria with very low allelic frequency and high protein impact, revealed five novel variants in IRF2BP2. In addition, we isolated both wild-type and mutated allele of the cDNA from one of the families.ResultsIn this study, we report five novel loss-of-function (LoF) mutations in IRF2BP2 that likely cause primary immunodeficiency, with CVID as more frequent phenotype, variable expression of inflammatory gastrointestinal features, and one patient with predisposition of viral infection. All identified variants were frameshift changes, and one of them was a large deletion located on chromosome 1q42, which includes the whole sequence of IRF2BP2, among other genes. Both de novo and dominant modes of inheritance were observed in the families here presented, as well as incomplete penetrance.ConclusionsWe describe novel variants in a delimited low-complex region, which may be considered a hotspot in IRF2BP2. Moreover, this is the first time that a large CNV in IRF2BP2 has been reported to cause CVID. The distinct mechanisms than LoF in IRF2BP2 could cause different phenotype compared with the mainly described. Further investigations are necessary to comprehend the regulatory mechanisms of IRF2BP2, which could be under variable expression of the disease. IRF2BP2 CVID colitis primary immunodeficiency loss-of-function mutations Immunologic diseases. Allergy Emilia Maneiro Pampín verfasserin aut Maite García Ramos verfasserin aut María José Acuña Pérez verfasserin aut Nerea Paz Gandiaga verfasserin aut Laura Minguell Domingo verfasserin aut Olga Calavia verfasserin aut Pere Soler-Palacin verfasserin aut Pere Soler-Palacin verfasserin aut Roger Colobran verfasserin aut Roger Colobran verfasserin aut Roger Colobran verfasserin aut Roger Colobran verfasserin aut Erika M. Novoa Bolívar verfasserin aut Javier Gonzalo Ocejo Vinyals verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 14(2023) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:14 year:2023 https://doi.org/10.3389/fimmu.2023.1279171 kostenfrei https://doaj.org/article/de4d55f278164823b4e8b63927542c96 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2023.1279171/full kostenfrei https://doaj.org/toc/1664-3224 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_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_2014 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 2023
language	English
source	In Frontiers in Immunology 14(2023) volume:14 year:2023
sourceStr	In Frontiers in Immunology 14(2023) volume:14 year:2023
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	IRF2BP2 CVID colitis primary immunodeficiency loss-of-function mutations Immunologic diseases. Allergy
isfreeaccess_bool	true
container_title	Frontiers in Immunology
authorswithroles_txt_mv	José María García-Aznar @@aut@@ Emilia Maneiro Pampín @@aut@@ Maite García Ramos @@aut@@ María José Acuña Pérez @@aut@@ Nerea Paz Gandiaga @@aut@@ Laura Minguell Domingo @@aut@@ Olga Calavia @@aut@@ Pere Soler-Palacin @@aut@@ Roger Colobran @@aut@@ Erika M. Novoa Bolívar @@aut@@ Javier Gonzalo Ocejo Vinyals @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
hierarchy_top_id	657998354
id	DOAJ09185783X
language_de	englisch
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As previous studies have described, the haploinsufficiency of this interferon transcriptional corepressors leads to the development of CVID. Very recently, a more accurate phenotype produced by truncating variants in this gene has been defined, manifesting CVID with gastrointestinal inflammatory symptoms and autoimmune manifestations.MethodsWe analyzed 5 index cases with suspected primary immunodeficiency by high throughput sequencing. They were submitted for a genetic test with a panel of genes associated with immune system diseases, including IRF2BP2. The screening of SNVs, indels and CNVs fulfilling the criteria with very low allelic frequency and high protein impact, revealed five novel variants in IRF2BP2. In addition, we isolated both wild-type and mutated allele of the cDNA from one of the families.ResultsIn this study, we report five novel loss-of-function (LoF) mutations in IRF2BP2 that likely cause primary immunodeficiency, with CVID as more frequent phenotype, variable expression of inflammatory gastrointestinal features, and one patient with predisposition of viral infection. All identified variants were frameshift changes, and one of them was a large deletion located on chromosome 1q42, which includes the whole sequence of IRF2BP2, among other genes. Both de novo and dominant modes of inheritance were observed in the families here presented, as well as incomplete penetrance.ConclusionsWe describe novel variants in a delimited low-complex region, which may be considered a hotspot in IRF2BP2. Moreover, this is the first time that a large CNV in IRF2BP2 has been reported to cause CVID. 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callnumber-first	R - Medicine
author	José María García-Aznar
spellingShingle	José María García-Aznar misc RC581-607 misc IRF2BP2 misc CVID misc colitis misc primary immunodeficiency misc loss-of-function mutations misc Immunologic diseases. Allergy Novel frameshift variants expand the map of the genetic defects in IRF2BP2
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topic_title	RC581-607 Novel frameshift variants expand the map of the genetic defects in IRF2BP2 IRF2BP2 CVID colitis primary immunodeficiency loss-of-function mutations
topic	misc RC581-607 misc IRF2BP2 misc CVID misc colitis misc primary immunodeficiency misc loss-of-function mutations misc Immunologic diseases. Allergy
topic_unstemmed	misc RC581-607 misc IRF2BP2 misc CVID misc colitis misc primary immunodeficiency misc loss-of-function mutations misc Immunologic diseases. Allergy
topic_browse	misc RC581-607 misc IRF2BP2 misc CVID misc colitis misc primary immunodeficiency misc loss-of-function mutations misc Immunologic diseases. Allergy
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title	Novel frameshift variants expand the map of the genetic defects in IRF2BP2
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title_full	Novel frameshift variants expand the map of the genetic defects in IRF2BP2
author_sort	José María García-Aznar
journal	Frontiers in Immunology
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author_browse	José María García-Aznar Emilia Maneiro Pampín Maite García Ramos María José Acuña Pérez Nerea Paz Gandiaga Laura Minguell Domingo Olga Calavia Pere Soler-Palacin Roger Colobran Erika M. Novoa Bolívar Javier Gonzalo Ocejo Vinyals
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author-letter	José María García-Aznar
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title_sort	novel frameshift variants expand the map of the genetic defects in irf2bp2
callnumber	RC581-607
title_auth	Novel frameshift variants expand the map of the genetic defects in IRF2BP2
abstract	BackgroundAt present, the knowledge about disease-causing mutations in IRF2BP2 is very limited because only a few patients affected by this condition have been reported. As previous studies have described, the haploinsufficiency of this interferon transcriptional corepressors leads to the development of CVID. Very recently, a more accurate phenotype produced by truncating variants in this gene has been defined, manifesting CVID with gastrointestinal inflammatory symptoms and autoimmune manifestations.MethodsWe analyzed 5 index cases with suspected primary immunodeficiency by high throughput sequencing. They were submitted for a genetic test with a panel of genes associated with immune system diseases, including IRF2BP2. The screening of SNVs, indels and CNVs fulfilling the criteria with very low allelic frequency and high protein impact, revealed five novel variants in IRF2BP2. In addition, we isolated both wild-type and mutated allele of the cDNA from one of the families.ResultsIn this study, we report five novel loss-of-function (LoF) mutations in IRF2BP2 that likely cause primary immunodeficiency, with CVID as more frequent phenotype, variable expression of inflammatory gastrointestinal features, and one patient with predisposition of viral infection. All identified variants were frameshift changes, and one of them was a large deletion located on chromosome 1q42, which includes the whole sequence of IRF2BP2, among other genes. Both de novo and dominant modes of inheritance were observed in the families here presented, as well as incomplete penetrance.ConclusionsWe describe novel variants in a delimited low-complex region, which may be considered a hotspot in IRF2BP2. Moreover, this is the first time that a large CNV in IRF2BP2 has been reported to cause CVID. The distinct mechanisms than LoF in IRF2BP2 could cause different phenotype compared with the mainly described. Further investigations are necessary to comprehend the regulatory mechanisms of IRF2BP2, which could be under variable expression of the disease.
abstractGer	BackgroundAt present, the knowledge about disease-causing mutations in IRF2BP2 is very limited because only a few patients affected by this condition have been reported. As previous studies have described, the haploinsufficiency of this interferon transcriptional corepressors leads to the development of CVID. Very recently, a more accurate phenotype produced by truncating variants in this gene has been defined, manifesting CVID with gastrointestinal inflammatory symptoms and autoimmune manifestations.MethodsWe analyzed 5 index cases with suspected primary immunodeficiency by high throughput sequencing. They were submitted for a genetic test with a panel of genes associated with immune system diseases, including IRF2BP2. The screening of SNVs, indels and CNVs fulfilling the criteria with very low allelic frequency and high protein impact, revealed five novel variants in IRF2BP2. In addition, we isolated both wild-type and mutated allele of the cDNA from one of the families.ResultsIn this study, we report five novel loss-of-function (LoF) mutations in IRF2BP2 that likely cause primary immunodeficiency, with CVID as more frequent phenotype, variable expression of inflammatory gastrointestinal features, and one patient with predisposition of viral infection. All identified variants were frameshift changes, and one of them was a large deletion located on chromosome 1q42, which includes the whole sequence of IRF2BP2, among other genes. Both de novo and dominant modes of inheritance were observed in the families here presented, as well as incomplete penetrance.ConclusionsWe describe novel variants in a delimited low-complex region, which may be considered a hotspot in IRF2BP2. Moreover, this is the first time that a large CNV in IRF2BP2 has been reported to cause CVID. The distinct mechanisms than LoF in IRF2BP2 could cause different phenotype compared with the mainly described. Further investigations are necessary to comprehend the regulatory mechanisms of IRF2BP2, which could be under variable expression of the disease.
abstract_unstemmed	BackgroundAt present, the knowledge about disease-causing mutations in IRF2BP2 is very limited because only a few patients affected by this condition have been reported. As previous studies have described, the haploinsufficiency of this interferon transcriptional corepressors leads to the development of CVID. Very recently, a more accurate phenotype produced by truncating variants in this gene has been defined, manifesting CVID with gastrointestinal inflammatory symptoms and autoimmune manifestations.MethodsWe analyzed 5 index cases with suspected primary immunodeficiency by high throughput sequencing. They were submitted for a genetic test with a panel of genes associated with immune system diseases, including IRF2BP2. The screening of SNVs, indels and CNVs fulfilling the criteria with very low allelic frequency and high protein impact, revealed five novel variants in IRF2BP2. In addition, we isolated both wild-type and mutated allele of the cDNA from one of the families.ResultsIn this study, we report five novel loss-of-function (LoF) mutations in IRF2BP2 that likely cause primary immunodeficiency, with CVID as more frequent phenotype, variable expression of inflammatory gastrointestinal features, and one patient with predisposition of viral infection. All identified variants were frameshift changes, and one of them was a large deletion located on chromosome 1q42, which includes the whole sequence of IRF2BP2, among other genes. Both de novo and dominant modes of inheritance were observed in the families here presented, as well as incomplete penetrance.ConclusionsWe describe novel variants in a delimited low-complex region, which may be considered a hotspot in IRF2BP2. Moreover, this is the first time that a large CNV in IRF2BP2 has been reported to cause CVID. The distinct mechanisms than LoF in IRF2BP2 could cause different phenotype compared with the mainly described. Further investigations are necessary to comprehend the regulatory mechanisms of IRF2BP2, which could be under variable expression of the disease.
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title_short	Novel frameshift variants expand the map of the genetic defects in IRF2BP2
url	https://doi.org/10.3389/fimmu.2023.1279171 https://doaj.org/article/de4d55f278164823b4e8b63927542c96 https://www.frontiersin.org/articles/10.3389/fimmu.2023.1279171/full https://doaj.org/toc/1664-3224
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author2	Emilia Maneiro Pampín Maite García Ramos María José Acuña Pérez Nerea Paz Gandiaga Laura Minguell Domingo Olga Calavia Pere Soler-Palacin Roger Colobran Erika M. Novoa Bolívar Javier Gonzalo Ocejo Vinyals
author2Str	Emilia Maneiro Pampín Maite García Ramos María José Acuña Pérez Nerea Paz Gandiaga Laura Minguell Domingo Olga Calavia Pere Soler-Palacin Roger Colobran Erika M. Novoa Bolívar Javier Gonzalo Ocejo Vinyals
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up_date	2024-07-03T22:41:10.635Z
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score	7.402011

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Novel frameshift variants expand the map of the genetic defects in IRF2BP2

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