{"title":"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。","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":"{\"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}","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}
Exome Sequencing Reveals Novel Variants in Genetic Skeletal Disorders: Insights From a Cohort in Southwest Iran.
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.
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