The impact of rare and low-frequency genetic variants in common variable immunodeficiency (CVID)

Abstract Next Generation Sequencing (NGS) has uncovered hundreds of common and rare genetic variants involved in complex and rare diseases including immune deficiencies in both an autosomal recessive and autosomal dominant pattern. These rare variants however, cannot be classified clinically, and co...

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Autores principales:	Atil Bisgin, Ozge Sonmezler, Ibrahim Boga, Mustafa Yilmaz
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9860c16dc312496c9bd9413bcbfdcdeb
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spelling	oai:doaj.org-article:9860c16dc312496c9bd9413bcbfdcdeb2021-12-02T18:03:07ZThe impact of rare and low-frequency genetic variants in common variable immunodeficiency (CVID)10.1038/s41598-021-87898-12045-2322https://doaj.org/article/9860c16dc312496c9bd9413bcbfdcdeb2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87898-1https://doaj.org/toc/2045-2322Abstract Next Generation Sequencing (NGS) has uncovered hundreds of common and rare genetic variants involved in complex and rare diseases including immune deficiencies in both an autosomal recessive and autosomal dominant pattern. These rare variants however, cannot be classified clinically, and common variants only marginally contribute to disease susceptibility. In this study, we evaluated the multi-gene panel results of Common Variable Immunodeficiency (CVID) patients and argue that rare variants located in different genes play a more prominent role in disease susceptibility and/or etiology. We performed NGS on DNA extracted from the peripheral blood leukocytes from 103 patients using a panel of 19 CVID-related genes: CARD11, CD19, CD81, ICOS, CTLA4, CXCR4, GATA2, CR2, IRF2BP2, MOGS, MS4A1, NFKB1, NFKB2, PLCG2, TNFRSF13B, TNFRSF13C, TNFSF12, TRNT1 and TTC37. Detected variants were evaluated and classified based on their impact, pathogenicity classification and population frequency as well as the frequency within our study group. NGS revealed 112 different (a total of 227) variants with under 10% population frequency in 103 patients of which 22(19.6%) were classified as benign, 29(25.9%) were classified as likely benign, 4(3.6%) were classified as likely pathogenic and 2(1.8%) were classified as pathogenic. Moreover, 55(49.1%) of the variants were classified as variants of uncertain significance. We also observed different variant frequencies when compared to population frequency databases. Case–control data is not sufficient to unravel the genetic etiology of immune deficiencies. Thus, it is important to understand the incidence of co-occurrence of two or more rare variants to aid in illuminating their potential roles in the pathogenesis of immune deficiencies.Atil BisginOzge SonmezlerIbrahim BogaMustafa YilmazNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Atil Bisgin Ozge Sonmezler Ibrahim Boga Mustafa Yilmaz The impact of rare and low-frequency genetic variants in common variable immunodeficiency (CVID)
description	Abstract Next Generation Sequencing (NGS) has uncovered hundreds of common and rare genetic variants involved in complex and rare diseases including immune deficiencies in both an autosomal recessive and autosomal dominant pattern. These rare variants however, cannot be classified clinically, and common variants only marginally contribute to disease susceptibility. In this study, we evaluated the multi-gene panel results of Common Variable Immunodeficiency (CVID) patients and argue that rare variants located in different genes play a more prominent role in disease susceptibility and/or etiology. We performed NGS on DNA extracted from the peripheral blood leukocytes from 103 patients using a panel of 19 CVID-related genes: CARD11, CD19, CD81, ICOS, CTLA4, CXCR4, GATA2, CR2, IRF2BP2, MOGS, MS4A1, NFKB1, NFKB2, PLCG2, TNFRSF13B, TNFRSF13C, TNFSF12, TRNT1 and TTC37. Detected variants were evaluated and classified based on their impact, pathogenicity classification and population frequency as well as the frequency within our study group. NGS revealed 112 different (a total of 227) variants with under 10% population frequency in 103 patients of which 22(19.6%) were classified as benign, 29(25.9%) were classified as likely benign, 4(3.6%) were classified as likely pathogenic and 2(1.8%) were classified as pathogenic. Moreover, 55(49.1%) of the variants were classified as variants of uncertain significance. We also observed different variant frequencies when compared to population frequency databases. Case–control data is not sufficient to unravel the genetic etiology of immune deficiencies. Thus, it is important to understand the incidence of co-occurrence of two or more rare variants to aid in illuminating their potential roles in the pathogenesis of immune deficiencies.
format	article
author	Atil Bisgin Ozge Sonmezler Ibrahim Boga Mustafa Yilmaz
author_facet	Atil Bisgin Ozge Sonmezler Ibrahim Boga Mustafa Yilmaz
author_sort	Atil Bisgin
title	The impact of rare and low-frequency genetic variants in common variable immunodeficiency (CVID)
title_short	The impact of rare and low-frequency genetic variants in common variable immunodeficiency (CVID)
title_full	The impact of rare and low-frequency genetic variants in common variable immunodeficiency (CVID)
title_fullStr	The impact of rare and low-frequency genetic variants in common variable immunodeficiency (CVID)
title_full_unstemmed	The impact of rare and low-frequency genetic variants in common variable immunodeficiency (CVID)
title_sort	impact of rare and low-frequency genetic variants in common variable immunodeficiency (cvid)
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9860c16dc312496c9bd9413bcbfdcdeb
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The impact of rare and low-frequency genetic variants in common variable immunodeficiency (CVID)

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