Fedick Anastasia M, Jalas Chaim, Swaroop Ananya, Smouha Eric E, Webb Bryn D
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Bonei Olam, Center for Rare Jewish Genetic Disorders, Brooklyn, NY, USA.
Appl Clin Genet. 2016 Aug 31;9:141-6. doi: 10.2147/TACG.S113828. eCollection 2016.
Mutations in the OTOF gene have previously been shown to cause nonsyndromic prelingual deafness (DFNB9, OMIM 601071) as well as auditory neuropathy/dys-synchrony. In this study, the OTOF NM_194248.2 c.5332G>T, p.Val1778Phe variant was identified in a large Ashkenazi Jewish family as the causative variant in four siblings with hearing loss. Our analysis reveals a carrier frequency of the OTOF c.5332G>T, p.Val1778Phe variant of 1.27% in the Ashkenazi Jewish population, suggesting that this variant may be a significant contributor to nonsyndromic sensorineural hearing loss and should be considered for inclusion in targeted hearing loss panels for this population. Of note, the degree of hearing loss associated with this phenotype ranged from mild to moderately severe, with two of the four siblings not known to have hearing loss until they were genotyped and underwent pure tone audiometry and auditory brainstem response testing. The phenotypic variability along with the auditory neuropathy/dys-synchrony, which allows for the production of otoacoustic emissions, supports that nonsyndromic hearing loss caused by OTOF mutations may be much more common in the Ashkenazi Jewish population than currently appreciated due to a lack of diagnosis.
此前已表明，OTOF基因突变会导致非综合征性语前聋（DFNB9，OMIM 601071）以及听觉神经病/不同步。在本研究中，在一个庞大的阿什肯纳兹犹太家族中，鉴定出OTOF NM_194248.2 c.5332G>T，p.Val1778Phe变异体是四名听力损失兄弟姐妹的致病变异体。我们的分析显示，阿什肯纳兹犹太人群中OTOF c.5332G>T，p.Val1778Phe变异体的携带频率为1.27%，这表明该变异体可能是导致非综合征性感音神经性听力损失的一个重要因素，应考虑将其纳入该人群的靶向听力损失检测组。值得注意的是，与该表型相关的听力损失程度从轻度到中度重度不等，四名兄弟姐妹中有两名在进行基因分型、纯音听力测定和听觉脑干反应测试之前，一直未被发现有听力损失。这种表型变异性以及听觉神经病/不同步（其允许耳声发射的产生）表明，由于缺乏诊断，OTOF突变导致的非综合征性听力损失在阿什肯纳兹犹太人群中可能比目前所认识到的更为常见。
