Hereditary hearing loss is a heterogeneous group of complex disorders with an overall incidence of one in every 500 newborns presented as syndromic and non-syndromic forms. Cadherin-related 23 (CDH23) is one of the listed deafness causative genes. It is found to be expressed in the stereocilia of hair cells and in the retina photoreceptor cells. Defective CDH23 have been associated mostly with prelingual severe-to-profound sensorineural hearing loss (SNHL) in either syndromic (USH1D) or non-syndromic SNHL (DFNB12) deafness. The purpose of this study was to identify causative mutations in an Omani family diagnosed with severe-profound sensorineural hearing loss by whole exome sequencing technique and analyzing the detected variant in silico for pathogenicity using several in silico mutation prediction software. A novel homozygous missense variant, c.A7436C (p. D2479A), in exon 53 of CDH23 was detected in the family while the control samples were all negative for the detected variant. In silico mutation prediction analysis showed the novel substituted D2479A to be deleterious and protein destabilizing mutation at a conserved site on CDH23 protein. In silico mutation prediction analysis might be used as a useful molecular diagnostic tool benefiting both genetic counseling and mutation verification. The aspartic acid 2479 alanine missense substitution might be the main disease-causing mutation that damages CDH23 function and could be used as a genetic hearing loss marker for this particular Omani family.

中文翻译：

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在计算机分析中对阿曼家族中有听力损失的Cadherin23基因中一个新的致病突变进行分析

遗传性听力损失是一组复杂的异质性疾病，每500例新生儿中，总发病率为综合症和非综合症形式。钙黏着蛋白相关23（CDH23）是所列的耳聋致病基因之一。发现它在毛细胞的立体纤毛和视网膜感光细胞中表达。CDH23缺陷主要与综合征性（USH1D）或非综合征性SNHL（DFNB12）耳聋的舌前严重至严重的感觉神经性听力损失（SNHL）相关。这项研究的目的是通过全外显子组测序技术确定被诊断为严重严重感觉神经性听力损失的阿曼家族的致病性突变，并使用几种计算机突变预测软件分析计算机中检测到的变异体的致病性。一种新型的纯合错义变体，c.A7436C（p。D2479A），在该家族中检测到CDH23的第53外显子，而对照样品均对检测到的变体阴性。计算机突变预测分析显示，新取代的D2479A具有有害性，并且CDH23蛋白的保守位点处的蛋白不稳定。电子计算机中的突变预测分析可以用作有益的遗传诊断和突变验证的分子诊断工具。天门冬氨酸2479丙氨酸错义替换可能是导致CDH23功能受损的主要致病突变，可用作该特定阿曼家族的遗传性听力损失标记。在计算机上进行的突变预测分析表明，新取代的D2479A在CDH23蛋白的保守位点是有害的，并且使蛋白质不稳定。电子计算机中的突变预测分析可以用作有益的遗传诊断和突变验证的分子诊断工具。天门冬氨酸2479丙氨酸错义替换可能是导致CDH23功能受损的主要致病突变，可用作该特定阿曼家族的遗传性听力损失标记。计算机突变预测分析显示，新取代的D2479A具有有害性，并且CDH23蛋白的保守位点处的蛋白不稳定。电子计算机中的突变预测分析可以用作有益的遗传诊断和突变验证的分子诊断工具。天门冬氨酸2479丙氨酸错义替换可能是导致CDH23功能受损的主要致病突变，可用作该特定阿曼家族的遗传性听力损失标记。