A Novel Homozygous Loss-of-Function Variant in GPR156 Delineates Non-syndromic Hearing Loss.

IF 1.6 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemical Genetics Pub Date : 2025-01-06 DOI:10.1007/s10528-024-11019-6

M Muaaz Aslam, Safdar Abbas, Shoaib Nawaz, Gohar Zaman, Ishtiaq Ahmed, Misbahuddin Rafeeq, Ziaullah M Sain, Alaa Hamed Habib, Muhammad Umair, Khadim Shah

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Abstract

Non-syndromic hearing loss (NSHL) is a genetically heterogeneous disorder accounting for almost 70% of the total congenital hearing loss. The implementation of rapid advanced sequencing methods has significantly contributed to the correct molecular diagnosis for several rare genetic disorders, including NHSL. Features of two probands with NHSL were clinically and genetically evaluated. One of the affected individuals was subjected to exome sequencing (ES) using standard methods. 3D protein modeling was performed to check the effect of mutation on the protein structure. ES data analysis revealed a homozygous nonsense variant [c.1144A > T; p.Lys382*] within the GPR156 gene (NM_153002.3) associated with rare NSHL. Sanger sequencing supported its recessive segregation within the family. The in silico predictions and 3D protein modeling further affirmed its disease-causing nature. The present study reported a nonsense variant in the GPR156 and its association with NSHL susceptibility, which requires further studies to unveil its key role and disease-related pathophysiology.

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一种新的GPR156纯合子功能丧失变体描述了非综合征性听力损失。

非综合征性听力损失（NSHL）是一种遗传异质性疾病，占先天性听力损失的近70%。快速先进测序方法的实施为包括NHSL在内的几种罕见遗传疾病的正确分子诊断做出了重大贡献。对2例NHSL先证者的临床和遗传学特征进行评价。其中一个受影响的个体使用标准方法进行外显子组测序（ES）。进行三维蛋白质建模以检查突变对蛋白质结构的影响。ES数据分析显示一个纯合无义变异[c.1144A > T；与罕见NSHL相关的GPR156基因（NM_153002.3）中的p.Lys382*]。桑格测序法支持家族内部的隐性隔离。计算机预测和三维蛋白质模型进一步证实了其致病性质。本研究报道了GPR156的无义变异及其与NSHL易感性的关联，这需要进一步的研究来揭示其关键作用和疾病相关的病理生理。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biochemical Genetics 生物-生化与分子生物学

CiteScore

3.90

自引率

0.00%

发文量

133

审稿时长

4.8 months

期刊介绍： Biochemical Genetics welcomes original manuscripts that address and test clear scientific hypotheses, are directed to a broad scientific audience, and clearly contribute to the advancement of the field through the use of sound sampling or experimental design, reliable analytical methodologies and robust statistical analyses. Although studies focusing on particular regions and target organisms are welcome, it is not the journal’s goal to publish essentially descriptive studies that provide results with narrow applicability, or are based on very small samples or pseudoreplication. Rather, Biochemical Genetics welcomes review articles that go beyond summarizing previous publications and create added value through the systematic analysis and critique of the current state of knowledge or by conducting meta-analyses. Methodological articles are also within the scope of Biological Genetics, particularly when new laboratory techniques or computational approaches are fully described and thoroughly compared with the existing benchmark methods. Biochemical Genetics welcomes articles on the following topics: Genomics; Proteomics; Population genetics; Phylogenetics; Metagenomics; Microbial genetics; Genetics and evolution of wild and cultivated plants; Animal genetics and evolution; Human genetics and evolution; Genetic disorders; Genetic markers of diseases; Gene technology and therapy; Experimental and analytical methods; Statistical and computational methods.