{"title":"一个中国家庭先天性非综合征性感音神经性听力损失相关耳胶蛋白样基因(OTOGL)双等位基因突变","authors":"Xiang Dai, Jun Li, Xijiang Hu, Wenqian Cai","doi":"10.1002/mgg3.70122","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Hearing loss, characterized by significant genetic heterogeneity, is a widespread global disorder. Mutations in the OTOG and OTOGL genes have recently been implicated in non-syndromic sensorineural hearing loss. However, the mutation spectrum of OTOGL and its functional relevance remain incompletely understood.</p><p><strong>Methods: </strong>We investigated a Chinese family with unexplained hearing loss using whole-exome sequencing. Compound heterozygous mutations in the OTOGL gene were identified and validated through Sanger sequencing. The proband's clinical features were assessed through audiological evaluations, and genotype-phenotype correlation analysis was conducted. Additionally, single-cell RNA sequencing analysis of the inner ear was performed to explore OTOGL's expression profile in auditory-related cell types.</p><p><strong>Results: </strong>Two compound heterozygous mutations in the OTOGL gene (p.Ile34Val and p.Phe319del) were identified in the proband, a 6-year-old boy with moderate congenital hearing loss. These mutations are predicted to be pathogenic and may explain the observed phenotype. Single-cell RNA sequencing revealed specific OTOGL expression in key auditory-related cell types, providing insights into its developmental and functional roles in the inner ear.</p><p><strong>Conclusion: </strong>The findings have marked implications for molecular diagnosis and genetic counseling, potentially guiding more personalized treatment and intervention strategies in clinical practice.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 7","pages":"e70122"},"PeriodicalIF":1.5000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274630/pdf/","citationCount":"0","resultStr":"{\"title\":\"Biallelic Mutations in the Otogelin-Like Gene (OTOGL) Associated With Congenital Non-Syndromic Sensorineural Hearing Loss in a Chinese Family.\",\"authors\":\"Xiang Dai, Jun Li, Xijiang Hu, Wenqian Cai\",\"doi\":\"10.1002/mgg3.70122\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Hearing loss, characterized by significant genetic heterogeneity, is a widespread global disorder. Mutations in the OTOG and OTOGL genes have recently been implicated in non-syndromic sensorineural hearing loss. However, the mutation spectrum of OTOGL and its functional relevance remain incompletely understood.</p><p><strong>Methods: </strong>We investigated a Chinese family with unexplained hearing loss using whole-exome sequencing. Compound heterozygous mutations in the OTOGL gene were identified and validated through Sanger sequencing. The proband's clinical features were assessed through audiological evaluations, and genotype-phenotype correlation analysis was conducted. Additionally, single-cell RNA sequencing analysis of the inner ear was performed to explore OTOGL's expression profile in auditory-related cell types.</p><p><strong>Results: </strong>Two compound heterozygous mutations in the OTOGL gene (p.Ile34Val and p.Phe319del) were identified in the proband, a 6-year-old boy with moderate congenital hearing loss. These mutations are predicted to be pathogenic and may explain the observed phenotype. Single-cell RNA sequencing revealed specific OTOGL expression in key auditory-related cell types, providing insights into its developmental and functional roles in the inner ear.</p><p><strong>Conclusion: </strong>The findings have marked implications for molecular diagnosis and genetic counseling, potentially guiding more personalized treatment and intervention strategies in clinical practice.</p>\",\"PeriodicalId\":18852,\"journal\":{\"name\":\"Molecular Genetics & Genomic Medicine\",\"volume\":\"13 7\",\"pages\":\"e70122\"},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2025-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274630/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Genetics & Genomic Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/mgg3.70122\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Genetics & Genomic Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/mgg3.70122","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
Biallelic Mutations in the Otogelin-Like Gene (OTOGL) Associated With Congenital Non-Syndromic Sensorineural Hearing Loss in a Chinese Family.
Background: Hearing loss, characterized by significant genetic heterogeneity, is a widespread global disorder. Mutations in the OTOG and OTOGL genes have recently been implicated in non-syndromic sensorineural hearing loss. However, the mutation spectrum of OTOGL and its functional relevance remain incompletely understood.
Methods: We investigated a Chinese family with unexplained hearing loss using whole-exome sequencing. Compound heterozygous mutations in the OTOGL gene were identified and validated through Sanger sequencing. The proband's clinical features were assessed through audiological evaluations, and genotype-phenotype correlation analysis was conducted. Additionally, single-cell RNA sequencing analysis of the inner ear was performed to explore OTOGL's expression profile in auditory-related cell types.
Results: Two compound heterozygous mutations in the OTOGL gene (p.Ile34Val and p.Phe319del) were identified in the proband, a 6-year-old boy with moderate congenital hearing loss. These mutations are predicted to be pathogenic and may explain the observed phenotype. Single-cell RNA sequencing revealed specific OTOGL expression in key auditory-related cell types, providing insights into its developmental and functional roles in the inner ear.
Conclusion: The findings have marked implications for molecular diagnosis and genetic counseling, potentially guiding more personalized treatment and intervention strategies in clinical practice.
期刊介绍:
Molecular Genetics & Genomic Medicine is a peer-reviewed journal for rapid dissemination of quality research related to the dynamically developing areas of human, molecular and medical genetics. The journal publishes original research articles covering findings in phenotypic, molecular, biological, and genomic aspects of genomic variation, inherited disorders and birth defects. The broad publishing spectrum of Molecular Genetics & Genomic Medicine includes rare and common disorders from diagnosis to treatment. Examples of appropriate articles include reports of novel disease genes, functional studies of genetic variants, in-depth genotype-phenotype studies, genomic analysis of inherited disorders, molecular diagnostic methods, medical bioinformatics, ethical, legal, and social implications (ELSI), and approaches to clinical diagnosis. Molecular Genetics & Genomic Medicine provides a scientific home for next generation sequencing studies of rare and common disorders, which will make research in this fascinating area easily and rapidly accessible to the scientific community. This will serve as the basis for translating next generation sequencing studies into individualized diagnostics and therapeutics, for day-to-day medical care.
Molecular Genetics & Genomic Medicine publishes original research articles, reviews, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented.