Reiisi Somayeh, Tabatabaiefar Mohammad Amin, Sanati Mohammad Hosein, Chaleshtori Morteza Hashemzadeh
Department of Genetics, Faculty of Basic Sciences, University of Shahrekord, Shahrekord, Iran.
Medical Genetics Dept., Isfahan University of Medical Sciences, Isfahan, Iran.
Iran J Basic Med Sci. 2016 Jul;19(7):772-8.
Non-syndromic sensorineural hearing loss (NSHL) is a common disorder affecting approximately 1 in 500 newborns. This type of hearing loss is extremely heterogeneous and includes over 100 loci. Mutations in the GJB2 gene have been implicated in about half of autosomal recessive non-syndromic hearing loss (ARNSHL) cases, making this the most common cause of ARNSHL. For the latter form of deafness, most frequent genes proposed include GJB2, SLC26A4, MYO15A, OTOF, and CDH23 worldwide.
The aim of the present study was to define the role and frequency of MYO15A gene mutation in Iranian families. In this study 30 Iranian families were enrolled with over three deaf children and negative for GJB2. Then linkage analysis was performed by six DFNB3 short tandem repeat markers. Following that, mutation detection accomplished using DNA sequencing.
One family (3.33%) showed linkage to DFNB3 and a novel mutation was identified in the MYO15A gene (c.6442T>A): as the disease-causing mutation. Mutation co-segregated with hearing loss in the family but was not present in the 100 ethnicity-matched controls.
Our results confirmed that the hearing loss of the linked Iranian family was caused by a novel missense mutation in the MYO15A gene. This mutation is the first to be reported in the world and affects the first MyTH4 domain of the protein.
非综合征性感音神经性听力损失（NSHL）是一种常见疾病，约每500名新生儿中就有1例受其影响。这种类型的听力损失极其异质，包含100多个基因座。GJB2基因突变约占常染色体隐性非综合征性听力损失（ARNSHL）病例的一半，是ARNSHL最常见的病因。对于后一种耳聋形式，全球范围内提出的最常见基因包括GJB2、SLC26A4、MYO15A、OTOF和CDH23。
本研究的目的是确定MYO15A基因突变在伊朗家庭中的作用和频率。在本研究中，招募了30个有3名以上耳聋儿童且GJB2基因检测为阴性的伊朗家庭。然后通过6个DFNB3短串联重复标记进行连锁分析。随后，使用DNA测序进行突变检测。
一个家庭（3.33%）显示与DFNB3连锁，并在MYO15A基因中鉴定出一个新突变（c.6442T>A），作为致病突变。该突变在家庭中与听力损失共分离，但在100名种族匹配的对照中不存在。
我们的结果证实，该连锁的伊朗家庭的听力损失是由MYO15A基因中的一个新错义突变引起的。这个突变是世界上首次报道，影响该蛋白的第一个MyTH4结构域。
