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High-Frequency Exon Deletion of DNA Cross-Link Repair 1C Accounting for Severe Combined Immunodeficiency May Be Missed by Whole-Exome Sequencing

Next-generation sequencing (NGS) has been used to detect severe combined immunodeficiency (SCID) in patients, and some patients with DNA cross-link repair 1C (DCLRE1C) variants have been identified. Moreover, some compound variants, such as copy number variants (CNV) and single nucleotide variants (...

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Autores principales: Xiao, Feifan, Lu, Yulan, Wu, Bingbing, Liu, Bo, Li, Gang, Zhang, Ping, Zhou, Qinhua, Sun, Jinqiao, Wang, Huijun, Zhou, Wenhao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372405/
https://www.ncbi.nlm.nih.gov/pubmed/34421990
http://dx.doi.org/10.3389/fgene.2021.677748
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author Xiao, Feifan
Lu, Yulan
Wu, Bingbing
Liu, Bo
Li, Gang
Zhang, Ping
Zhou, Qinhua
Sun, Jinqiao
Wang, Huijun
Zhou, Wenhao
author_facet Xiao, Feifan
Lu, Yulan
Wu, Bingbing
Liu, Bo
Li, Gang
Zhang, Ping
Zhou, Qinhua
Sun, Jinqiao
Wang, Huijun
Zhou, Wenhao
author_sort Xiao, Feifan
collection PubMed
description Next-generation sequencing (NGS) has been used to detect severe combined immunodeficiency (SCID) in patients, and some patients with DNA cross-link repair 1C (DCLRE1C) variants have been identified. Moreover, some compound variants, such as copy number variants (CNV) and single nucleotide variants (SNV), have been reported. The purpose of this study was to expand the genetic data related to patients with SCID carrying the compound DCLRE1C variant. Whole-exome sequencing (WES) was performed for genetic analysis, and variants were verified by performing Sanger sequencing or quantitative PCR. Moreover, we searched PubMed and summarized the data of the reported variants. Four SCID patients with DCLRE1C variants were identified in this study. WES revealed a homozygous deletion in the DCLRE1C gene from exons 1–5 in patient 1, exons 1–3 deletion and a novel rare variant (c.92T>C, p.L31P) in patient 2, exons 1–3 deletion and a novel rare variant (c.328C>G, p.L110V) in patient 3, and exons 1–4 deletion and a novel frameshift variant (c.449dup, p.His151Alafs*20) in patient 4. Based on literature review, exons 1–3 was recognized as a hotspot region for deletion variation. Moreover, we found that compound variations (CNV + SNV) accounted for approximately 7% variations in all variants. When patients are screened for T-cell receptor excision circles (TRECs), NGS can be used to expand genetic testing. Deletion of the DCLRE1C gene should not be ignored when a variant has been found in patients with SCID.
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spelling pubmed-83724052021-08-19 High-Frequency Exon Deletion of DNA Cross-Link Repair 1C Accounting for Severe Combined Immunodeficiency May Be Missed by Whole-Exome Sequencing Xiao, Feifan Lu, Yulan Wu, Bingbing Liu, Bo Li, Gang Zhang, Ping Zhou, Qinhua Sun, Jinqiao Wang, Huijun Zhou, Wenhao Front Genet Genetics Next-generation sequencing (NGS) has been used to detect severe combined immunodeficiency (SCID) in patients, and some patients with DNA cross-link repair 1C (DCLRE1C) variants have been identified. Moreover, some compound variants, such as copy number variants (CNV) and single nucleotide variants (SNV), have been reported. The purpose of this study was to expand the genetic data related to patients with SCID carrying the compound DCLRE1C variant. Whole-exome sequencing (WES) was performed for genetic analysis, and variants were verified by performing Sanger sequencing or quantitative PCR. Moreover, we searched PubMed and summarized the data of the reported variants. Four SCID patients with DCLRE1C variants were identified in this study. WES revealed a homozygous deletion in the DCLRE1C gene from exons 1–5 in patient 1, exons 1–3 deletion and a novel rare variant (c.92T>C, p.L31P) in patient 2, exons 1–3 deletion and a novel rare variant (c.328C>G, p.L110V) in patient 3, and exons 1–4 deletion and a novel frameshift variant (c.449dup, p.His151Alafs*20) in patient 4. Based on literature review, exons 1–3 was recognized as a hotspot region for deletion variation. Moreover, we found that compound variations (CNV + SNV) accounted for approximately 7% variations in all variants. When patients are screened for T-cell receptor excision circles (TRECs), NGS can be used to expand genetic testing. Deletion of the DCLRE1C gene should not be ignored when a variant has been found in patients with SCID. Frontiers Media S.A. 2021-08-04 /pmc/articles/PMC8372405/ /pubmed/34421990 http://dx.doi.org/10.3389/fgene.2021.677748 Text en Copyright © 2021 Xiao, Lu, Wu, Liu, Li, Zhang, Zhou, Sun, Wang and Zhou. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Xiao, Feifan
Lu, Yulan
Wu, Bingbing
Liu, Bo
Li, Gang
Zhang, Ping
Zhou, Qinhua
Sun, Jinqiao
Wang, Huijun
Zhou, Wenhao
High-Frequency Exon Deletion of DNA Cross-Link Repair 1C Accounting for Severe Combined Immunodeficiency May Be Missed by Whole-Exome Sequencing
title High-Frequency Exon Deletion of DNA Cross-Link Repair 1C Accounting for Severe Combined Immunodeficiency May Be Missed by Whole-Exome Sequencing
title_full High-Frequency Exon Deletion of DNA Cross-Link Repair 1C Accounting for Severe Combined Immunodeficiency May Be Missed by Whole-Exome Sequencing
title_fullStr High-Frequency Exon Deletion of DNA Cross-Link Repair 1C Accounting for Severe Combined Immunodeficiency May Be Missed by Whole-Exome Sequencing
title_full_unstemmed High-Frequency Exon Deletion of DNA Cross-Link Repair 1C Accounting for Severe Combined Immunodeficiency May Be Missed by Whole-Exome Sequencing
title_short High-Frequency Exon Deletion of DNA Cross-Link Repair 1C Accounting for Severe Combined Immunodeficiency May Be Missed by Whole-Exome Sequencing
title_sort high-frequency exon deletion of dna cross-link repair 1c accounting for severe combined immunodeficiency may be missed by whole-exome sequencing
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372405/
https://www.ncbi.nlm.nih.gov/pubmed/34421990
http://dx.doi.org/10.3389/fgene.2021.677748
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