Recurrent variants in OTOF are significant contributors to prelingual nonsydromic hearing loss in Saudi patients.
Recurrent variants in OTOF are significant contributors to prelingual nonsydromic hearing loss in Saudi patients.
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DOI：
10.1038/gim.2017.143
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发表时间：
2018-04
期刊：
影响因子：
--
通讯作者：
Amr SS
中科院分区：
文献类型：
--
作者：
Almontashiri NAM;Alswaid A;Oza A;Al-Mazrou KA;Elrehim O;Tayoun AA;Rehm HL;Amr SS
沙特阿拉伯人口的听力损失比其他人口更为普遍；然而，该人群的全部遗传病因尚不清楚。我们报告了 33 名具有部落血统的沙特听力损失先证者的基因发现，这些先证者主要患有语前严重至极重度听力损失。测试在 2012 年至 2016 年期间进行，涉及初始 GJB2 序列和 GJB6-D13S1830 缺失筛选，阴性病例将反映到具有 70、71 或 87 个听力损失基因的下一代测序组中。 63% 的先证者获得了“阳性”结果，其中两种复发性 OTOF 变异（p.Glu57* 和 p.Arg1792His）占所有“阳性”病例的三分之一。第二个最常见的原因是 MYO7A 和 SLC26A4 的致病变异，每个变异均导致三个“阳性”病例。有趣的是，只有一个“阳性”诊断具有与 DFNB1 相关的原因，这是由于纯合 GJB6-D13S1830 缺失，并且没有检测到 GJB2 中的序列变异。我们的研究结果表明 OTOF 是沙特人群听力损失的潜在主要因素，同时强调 GJB2 的贡献较低，从而为沙特患者的临床测试策略提供了重要的考虑因素。需要对沙特患者进行进一步筛查，以确定该人群的遗传谱。
Hearing loss is more prevalent in the Saudi Arabian population than in other populations; however, the full range of genetic etiologies in this population is unknown. We report the genetic findings from 33 Saudi hearing-loss probands of tribal ancestry, with predominantly prelingual severe to profound hearing loss. Testing was performed over the course of 2012–2016, and involved initial GJB2 sequence and GJB6-D13S1830 deletion screening, with negative cases being reflexed to a next-generation sequencing panel with 70, 71, or 87 hearing-loss genes. A “positive” result was reached in 63% of probands, with two recurrent OTOF variants (p.Glu57* and p.Arg1792His) accountable for a third of all “positive” cases. The next most common cause was pathogenic variants in MYO7A and SLC26A4, each responsible for three “positive” cases. Interestingly, only one “positive” diagnosis had a DFNB1-related cause, due to a homozygous GJB6-D13S1830 deletion, and no sequence variants in GJB2 were detected. Our findings implicate OTOF as a potential major contributor to hearing loss in the Saudi population, while highlighting the low contribution of GJB2, thus offering important considerations for clinical testing strategies for Saudi patients. Further screening of Saudi patients is needed to characterize the genetic spectrum in this population.
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