DNA repair-related heritable photosensitivity syndromes: Mutation landscape in a multiethnic cohort of 17 multigenerational families with high degree of consanguinity

IF 3 3区 生物学 Q2 GENETICS & HEREDITY DNA Repair Pub Date : 2024-02-29 DOI:10.1016/j.dnarep.2024.103633
Amir Hozhabrpour , Marzieh Mojbafan , Fahimeh Palizban , Fatemeh vahidnezhad , Saeed Talebi , Maliheh Amani , Masoud Garshasbi , Anoosh Naghavi , Raziyeh Khalesi , Parvin Mansouri , Soheila Sotoudeh , Hamidreza Mahmoudi , Aida Varghaei , Maryam Daneshpazhooh , Fatemeh Karimi , Sirous Zeinali , Elnaz Kalamati , Jouni Uitto , Leila Youssefian , Hassan Vahidnezhad
{"title":"DNA repair-related heritable photosensitivity syndromes: Mutation landscape in a multiethnic cohort of 17 multigenerational families with high degree of consanguinity","authors":"Amir Hozhabrpour ,&nbsp;Marzieh Mojbafan ,&nbsp;Fahimeh Palizban ,&nbsp;Fatemeh vahidnezhad ,&nbsp;Saeed Talebi ,&nbsp;Maliheh Amani ,&nbsp;Masoud Garshasbi ,&nbsp;Anoosh Naghavi ,&nbsp;Raziyeh Khalesi ,&nbsp;Parvin Mansouri ,&nbsp;Soheila Sotoudeh ,&nbsp;Hamidreza Mahmoudi ,&nbsp;Aida Varghaei ,&nbsp;Maryam Daneshpazhooh ,&nbsp;Fatemeh Karimi ,&nbsp;Sirous Zeinali ,&nbsp;Elnaz Kalamati ,&nbsp;Jouni Uitto ,&nbsp;Leila Youssefian ,&nbsp;Hassan Vahidnezhad","doi":"10.1016/j.dnarep.2024.103633","DOIUrl":null,"url":null,"abstract":"<div><p>Inherited photosensitivity syndromes are a heterogeneous group of genetic skin disorders with tremendous phenotypic variability, characterized by photosensitivity and defective DNA repair, especially nucleotide excision repair. A cohort of 17 Iranian families with heritable photosensitivity syndromes was evaluated to identify their genetic defect. The patients' DNA was analyzed with either whole-exome sequencing or RNA sequencing (RNA-Seq). The interpretations of the genomic results were guided by genome-wide homozygosity mapping. Haplotype analysis was performed for cases with recurrent mutations. RNA-Seq, in addition to mutation detection, was also utilized to confirm the pathogenicity. Thirteen sequence variants, including six previously unreported pathogenic variants, were disclosed in 17 Iranian families, with <em>XPC</em> as the most common mutated gene in 10 families (59%). In one patient, RNA-Seq, as a first-tier diagnostic approach, revealed a non-canonical homozygous germline variant: <em>XPC</em>:c.413–9 T &gt; A. The Sashimi plot showed skipping of exon 4 with dramatic XPC down-expression. Haplotype analysis of <em>XPC</em>:c.2251–1 G&gt;C and <em>XPC</em>:1243 C&gt;T in four families showed common haplotypes of 1.7 Mb and 2.6 Mb, respectively, denoting a founder effect. Lastly, two extremely rare cases were presented in this report: a homozygous <em>UVSSA</em>:c .1990 C&gt;T was disclosed, and <em>ERCC2</em>-related cerebro-oculo-facio-skeletal (COFS) syndrome with an early childhood death. A direct comparison of our data with the results of previously reported cohorts demonstrates the international mutation landscape of DNA repair-related photosensitivity disorders, although population-specific differences were observed.</p></div>","PeriodicalId":300,"journal":{"name":"DNA Repair","volume":"136 ","pages":"Article 103633"},"PeriodicalIF":3.0000,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"DNA Repair","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1568786424000090","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0

Abstract

Inherited photosensitivity syndromes are a heterogeneous group of genetic skin disorders with tremendous phenotypic variability, characterized by photosensitivity and defective DNA repair, especially nucleotide excision repair. A cohort of 17 Iranian families with heritable photosensitivity syndromes was evaluated to identify their genetic defect. The patients' DNA was analyzed with either whole-exome sequencing or RNA sequencing (RNA-Seq). The interpretations of the genomic results were guided by genome-wide homozygosity mapping. Haplotype analysis was performed for cases with recurrent mutations. RNA-Seq, in addition to mutation detection, was also utilized to confirm the pathogenicity. Thirteen sequence variants, including six previously unreported pathogenic variants, were disclosed in 17 Iranian families, with XPC as the most common mutated gene in 10 families (59%). In one patient, RNA-Seq, as a first-tier diagnostic approach, revealed a non-canonical homozygous germline variant: XPC:c.413–9 T > A. The Sashimi plot showed skipping of exon 4 with dramatic XPC down-expression. Haplotype analysis of XPC:c.2251–1 G>C and XPC:1243 C>T in four families showed common haplotypes of 1.7 Mb and 2.6 Mb, respectively, denoting a founder effect. Lastly, two extremely rare cases were presented in this report: a homozygous UVSSA:c .1990 C>T was disclosed, and ERCC2-related cerebro-oculo-facio-skeletal (COFS) syndrome with an early childhood death. A direct comparison of our data with the results of previously reported cohorts demonstrates the international mutation landscape of DNA repair-related photosensitivity disorders, although population-specific differences were observed.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
DNA 修复相关遗传性光敏综合征:17 个多代高度近亲繁殖家庭的多种族队列中的突变情况
遗传性光敏感综合征是一组表型差异极大的异质性遗传性皮肤病,其特点是光敏感和 DNA 修复缺陷,尤其是核苷酸切除修复。我们对 17 个伊朗遗传性光敏综合征家族进行了评估,以确定其遗传缺陷。对患者的 DNA 进行了全外显子组测序或 RNA 测序(RNA-Seq)分析。基因组结果的解释以全基因组同源性图谱为指导。对有重复突变的病例进行了单倍型分析。除突变检测外,RNA-Seq 还用于确认致病性。在 17 个伊朗家族中发现了 13 个序列变异,其中包括 6 个以前未报道过的致病变异,在 10 个家族(59%)中,XPC 是最常见的变异基因。在一名患者中,作为一级诊断方法的 RNA-Seq 发现了一个非典型的同源种系变异:萨希米图显示,第 4 号外显子被跳过,XPC 表达急剧下降。对四个家系中的 XPC:c.2251-1 G>C 和 XPC:1243 C>T 进行的单倍型分析显示,常见的单倍型分别为 1.7 Mb 和 2.6 Mb,这表明存在创始效应。最后,本报告还介绍了两个极为罕见的病例:一个是同源的 UVSSA:c .1990 C>T,另一个是与 ERCC2 相关的脑-颅-面-骨(COFS)综合征,患者在童年早期死亡。将我们的数据与之前报告的队列结果进行直接比较,可以看出 DNA 修复相关光敏性疾病的国际突变情况,尽管也观察到了人群特异性差异。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
DNA Repair
DNA Repair 生物-毒理学
CiteScore
7.60
自引率
5.30%
发文量
91
审稿时长
59 days
期刊介绍: DNA Repair provides a forum for the comprehensive coverage of DNA repair and cellular responses to DNA damage. The journal publishes original observations on genetic, cellular, biochemical, structural and molecular aspects of DNA repair, mutagenesis, cell cycle regulation, apoptosis and other biological responses in cells exposed to genomic insult, as well as their relationship to human disease. DNA Repair publishes full-length research articles, brief reports on research, and reviews. The journal welcomes articles describing databases, methods and new technologies supporting research on DNA repair and responses to DNA damage. Letters to the Editor, hot topics and classics in DNA repair, historical reflections, book reviews and meeting reports also will be considered for publication.
期刊最新文献
Repair pathway coordination from gap filling by polβ and subsequent nick sealing by LIG1 or LIG3α governs BER efficiency at the downstream steps Targeting dePARylation in cancer therapy RNA damage and its implications in genome stability Advances in diagnostic and therapeutic applications of mismatch repair loss in cancer The hidden elephant: Modified abasic sites and their consequences
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1