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

IF 1.5 4区 医学 Q4 GENETICS & HEREDITY
Xiang Dai, Jun Li, Xijiang Hu, Wenqian Cai
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引用次数: 0

摘要

背景:听力损失是一种普遍存在的全球性疾病,具有显著的遗传异质性。OTOG和OTOGL基因的突变最近被认为与非综合征性感音神经性听力损失有关。然而,OTOGL的突变谱及其功能相关性仍不完全清楚。方法:我们使用全外显子组测序研究了一个中国不明原因听力损失家庭。通过Sanger测序鉴定并验证了OTOGL基因的复合杂合突变。通过听力学评估先证者的临床特征,并进行基因型-表型相关分析。此外,我们还进行了内耳单细胞RNA测序分析,以探索OTOGL在听觉相关细胞类型中的表达谱。结果:在6岁中度先天性听力损失男孩中,检测到OTOGL基因的两个复合杂合突变(p.i ile34val和p.p phe319del)。这些突变被认为是致病的,可以解释观察到的表型。单细胞RNA测序揭示了OTOGL在关键听觉相关细胞类型中的特异性表达,为其在内耳中的发育和功能作用提供了见解。结论:该研究结果对分子诊断和遗传咨询具有重要意义,可能指导临床实践中更个性化的治疗和干预策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.

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来源期刊
Molecular Genetics & Genomic Medicine
Molecular Genetics & Genomic Medicine Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
4.20
自引率
0.00%
发文量
241
审稿时长
14 weeks
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.
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