Genetic investigations on singleton school aged children reveal novel variants and new candidate genes for hearing loss

IF 3.8 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Scientific Reports Pub Date : 2024-09-13 DOI:10.1038/s41598-024-71407-1

Hina Khan, Fariha Muzaffar, Midhat Salman, Rasheeda Bashir, Go Hun Seo, Sadaf Naz

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Abstract

Hearing loss affects around 5% of the global population. Two preliminary studies have described genetic variants in sporadic individuals with hearing loss from Pakistan. Here we extend these studies to determine the spectrum of variants in a cohort of individuals with no previous history of hearing loss. Individuals with hearing loss born to consanguineous couples were identified from special schools. Audiograms were assessed. DNA from participants negative for GJB2 pathogenic variants was subjected to exome sequencing. Data were filtered to include variants with frequencies < 0.01 in the public databases. The effects of the missense variants on respective amino acids were analyzed by using PyMol software. Among the 44 participants, hearing loss was moderate for two individuals; 14 exhibited moderately-severe hearing loss while 25 had a severe degree of hearing loss. Hearing loss was reported to have been progressive in four participants and was currently profound in three participants. Variants were unambiguously identified in 17 genes, of which the majority affected SLC26A4. CDH23, MYO15A and OTOF were other significant contributors. Deleterious variants detected in two genes suggest new associations for hearing loss. Molecular characterization of hearing loss in our cohort revealed high genetic heterogeneity with a 75% diagnostic rate.

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对单胎学龄儿童的基因调查揭示了听力损失的新变异和新候选基因

全球约有 5%的人患有听力损失。两项初步研究描述了巴基斯坦零星听力损失患者的基因变异。在此，我们对这些研究进行了扩展，以确定既往无听力损失病史的人群中的变异谱。我们从特殊学校中发现了近亲结婚的听力损失患者。对听力图进行了评估。对GJB2致病变异阴性参与者的DNA进行外显子测序。数据经过过滤，以包括公共数据库中频率< 0.01的变异。使用 PyMol 软件分析了错义变异对相应氨基酸的影响。在44名参与者中，有2人的听力损失为中度；14人表现为中重度听力损失，25人听力损失为重度。据报告，4 名参与者的听力损失是渐进性的，3 名参与者的听力损失目前是极重度的。在 17 个基因中明确发现了变异，其中大多数影响 SLC26A4。CDH23、MYO15A 和 OTOF 是其他重要的致病基因。在两个基因中检测到的有害变异表明，听力损失与这些基因有新的关联。我们队列中听力损失的分子特征显示了高度的遗传异质性，诊断率为 75%。

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来源期刊

Scientific Reports Natural Science Disciplines-

CiteScore

7.50

自引率

4.30%

发文量

19567

审稿时长

3.9 months

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