Auditory Neuropathy Spectrum Disorder due to Two Novel Compound Heterozygous OTOF Mutations in Two Chinese Families
Auditory Neuropathy Spectrum Disorder due to Two Novel Compound Heterozygous OTOF Mutations in Two Chinese Families
复制标题
两个中国家系中两种新型复合杂合 OTOF 突变导致的听神经病谱系障碍
DOI：
10.1155/2019/9765276
复制
发表时间：
2019-11-18
影响因子：
3.1
通讯作者：
Kong, Wei-Jia
中科院分区：
文献类型：
--
作者：
Qiu, Yue;Chen, Sen;Kong, Wei-Jia
听神经病谱系障碍（ANSD），又称听神经病（AN），是一种独特的语前听力障碍。多达10%的聋哑婴儿和儿童受到这种疾病的影响。编码otoferlin的OTOF基因突变是先天性非综合征型ANSD的常见原因。迄今为止，根据人类基因突变数据库（HGMD），已在OTOF基因中鉴定出超过110种突变。新一代测序（NGS）结果显示，两名中国ANSD患者存在OTOF基因c.4748G>A/c.2523+1G>T和c.5248G>C/c.5098G>C的复合杂合突变。每个患者都有一个已知的致病突变（c.4748G>A或c.5098G>C）和一个新的突变（c.2523+1G>T或c.5248G>C）。不同物种的氨基酸序列比较分析表明，这些新突变位点的残基在进化上高度保守。这表明新的突变可能是患者疾病的原因。我们的发现扩展了OTOF突变谱，并进一步证实了OTOF基因在ANSD中的作用。
Auditory neuropathy spectrum disorder (ANSD), also called auditory neuropathy (AN), is a unique type of prelingual hearing impairment. Up to 10% of deaf infants and children are affected by this disease. Mutation of the OTOF gene which encodes otoferlin is the common cause of congenital nonsyndromic ANSD. To date, over 110 mutations have been identified in the OTOF gene according to the Human Gene Mutation Database (HGMD). Here, next-generation sequencing (NGS) revealed that the compound heterozygous mutations c.4748G>A/c.2523+1G>T and c.5248G>C/c.5098G>C of the OTOF gene were present in two Chinese ANSD patients. Each patient had a known pathogenic mutation (c.4748G>A or c.5098G>C) and a novel mutation (c.2523+1G>T or c.5248G>C). Comparative amino acid sequence analysis across different species revealed that the residues at these novel mutation sites are evolutionarily highly conservative. This indicated that the novel mutations were possible causes of the disorder in the patients. Our findings extend the OTOF mutation spectrum and further confirm the role of the OTOF gene in ANSD.