Exome Sequencing Reveals Novel Variants in Genetic Skeletal Disorders: Insights From a Cohort in Southwest Iran.

IF 2.3 3区 医学 Q2 GENETICS & HEREDITY
Rezvan Zabihi, Mina Zamani, Niloofar Chamanrou, Jawaher Zeighami, Tahere Seifi, Saeed Ashoori, Sahere Parvas, Tahere Yadegari, Fateme Mousavi, Elham Khajevandian, Moslem Sarvari, Kobra Shojaei, Pardis Nourbakhsh, Bijan Keikhaei, Majid Aminzadeh, Raha Ahmadi, Marzieh Mohammadi Anaei, Alireza Sedaghat, Alihossein Saberi, Mohammad Hamid, Golamreza Shariati, Hamid Galehdari
{"title":"Exome Sequencing Reveals Novel Variants in Genetic Skeletal Disorders: Insights From a Cohort in Southwest Iran.","authors":"Rezvan Zabihi, Mina Zamani, Niloofar Chamanrou, Jawaher Zeighami, Tahere Seifi, Saeed Ashoori, Sahere Parvas, Tahere Yadegari, Fateme Mousavi, Elham Khajevandian, Moslem Sarvari, Kobra Shojaei, Pardis Nourbakhsh, Bijan Keikhaei, Majid Aminzadeh, Raha Ahmadi, Marzieh Mohammadi Anaei, Alireza Sedaghat, Alihossein Saberi, Mohammad Hamid, Golamreza Shariati, Hamid Galehdari","doi":"10.1111/cge.70070","DOIUrl":null,"url":null,"abstract":"<p><p>Genetic skeletal disorders (GSDs) comprise a diverse group of disorders that affect bone development and homeostasis. In some areas of Iran, GSD occurs more frequently than in other places for still unknown reasons. The aim of this study was to characterize the genetic landscape of GSDs in a cohort from southwestern Iran using Exome sequencing (ES), with a focus on identifying pathogenic and likely pathogenic variants. Osteogenesis Imperfecta (OI) was the most prevalent disorder, with an unexpectedly high frequency of autosomal recessive subtypes, likely due to a high consanguinity rate (61.3%) in the cohort. Achondroplasia (ACH) was the second most common disease and, comparable to another population, the NM_000142.5:c.1138G>A, p.(Gly380Arg), was the most common variant in FGFR3. ES identified twenty novel and fifteen previously reported pathogenic variants in several genes associated with GSDs. We provide the first comprehensive ES-based molecular diagnosis of GSDs in an Iranian population and uncover novel pathogenic variants that expand the known spectrum of variants. The results underscore the importance of genetic testing in the diagnosis of rare skeletal diseases and highlight the need for targeted genetic counseling in populations with high consanguinity.</p>","PeriodicalId":10354,"journal":{"name":"Clinical Genetics","volume":" ","pages":""},"PeriodicalIF":2.3000,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Genetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/cge.70070","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0

Abstract

Genetic skeletal disorders (GSDs) comprise a diverse group of disorders that affect bone development and homeostasis. In some areas of Iran, GSD occurs more frequently than in other places for still unknown reasons. The aim of this study was to characterize the genetic landscape of GSDs in a cohort from southwestern Iran using Exome sequencing (ES), with a focus on identifying pathogenic and likely pathogenic variants. Osteogenesis Imperfecta (OI) was the most prevalent disorder, with an unexpectedly high frequency of autosomal recessive subtypes, likely due to a high consanguinity rate (61.3%) in the cohort. Achondroplasia (ACH) was the second most common disease and, comparable to another population, the NM_000142.5:c.1138G>A, p.(Gly380Arg), was the most common variant in FGFR3. ES identified twenty novel and fifteen previously reported pathogenic variants in several genes associated with GSDs. We provide the first comprehensive ES-based molecular diagnosis of GSDs in an Iranian population and uncover novel pathogenic variants that expand the known spectrum of variants. The results underscore the importance of genetic testing in the diagnosis of rare skeletal diseases and highlight the need for targeted genetic counseling in populations with high consanguinity.

外显子组测序揭示了遗传性骨骼疾病的新变异:来自伊朗西南部队列的见解。
遗传性骨骼疾病(gsd)包括影响骨骼发育和体内平衡的多种疾病。在伊朗的一些地区,由于未知的原因,GSD比其他地方发生得更频繁。本研究的目的是利用外显子组测序(ES)表征伊朗西南部队列中gsd的遗传景观,重点是鉴定致病性和可能致病性变异。成骨不全症(OI)是最普遍的疾病,常染色体隐性亚型的频率出乎意料地高,可能是由于在队列中的高血缘率(61.3%)。软骨发育不全(achdroplasia, ACH)是第二常见的疾病,与另一个人群相比,NM_000142.5:c。1138G >a, p.(Gly380Arg)是FGFR3中最常见的变体。在与gsd相关的几个基因中,ES鉴定出20个新的致病变异和15个先前报道的致病变异。我们在伊朗人群中提供了第一个全面的基于es的gsd分子诊断,并发现了新的致病变异,扩大了已知的变异谱。该结果强调了基因检测在罕见骨骼疾病诊断中的重要性,并强调了在高血缘人群中进行有针对性的遗传咨询的必要性。
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 求助全文
来源期刊
Clinical Genetics
Clinical Genetics 医学-遗传学
CiteScore
6.50
自引率
0.00%
发文量
175
审稿时长
3-8 weeks
期刊介绍: Clinical Genetics links research to the clinic, translating advances in our understanding of the molecular basis of genetic disease for the practising clinical geneticist. The journal publishes high quality research papers, short reports, reviews and mini-reviews that connect medical genetics research with clinical practice. Topics of particular interest are: • Linking genetic variations to disease • Genome rearrangements and disease • Epigenetics and disease • The translation of genotype to phenotype • Genetics of complex disease • Management/intervention of genetic diseases • Novel therapies for genetic diseases • Developmental biology, as it relates to clinical genetics • Social science research on the psychological and behavioural aspects of living with or being at risk of genetic disease
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信