Report of a Novel Splicing Mutation in the MYO15A Gene in a Patient With Sensorineural Hearing Loss and Spectrum of the MYO15A Mutations
Report of a Novel Splicing Mutation in the MYO15A Gene in a Patient With Sensorineural Hearing Loss and Spectrum of the MYO15A Mutations
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DOI：
10.1177/1179547619871907
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发表时间：
2019-09-22
影响因子：
1
通讯作者：
Rad, Isa Abdi
中科院分区：
文献类型：
--
作者：
Akbariazar, Elinaz;Vahabi, Ali;Rad, Isa Abdi
简介：常染色体隐性遗传性非综合征性听力损失（ARNSHL）是一种遗传异质性感音神经性疾病，在新生儿中的发病率约为1.4：1000。据报道，在ARNSHL患者中，包括MYO 15 A基因在内的60多个基因发生了突变。在本研究中，我们报告了一种新的MYO 15 A突变的临床外显子组测序和桑格测序证实在伊朗的一个血缘家庭ARNSHL.CASE介绍：一个22岁的女性先天性非综合征性感音神经性听力损失提到我们的医学遗传中心。她的父母是近亲，F = 1/16（第一堂兄弟姐妹），患者的临床检查排除了畸形特征。GJB 2和GJB 6基因的桑格测序结果为阴性，而GJB 2和GJB 6基因是ARNSHL最常见的病因。结果：我们在MYO 15 A基因中发现了一种新的纯合子变体（c.9611_9612+8delTGGTGAGCAT），该变体在密码子3204处开始的阅读框架中产生了移位。这种变异证实了桑格测序的病人，也在她的父母谁是杂zyotubes.Discussion：目前的结果表明，纯合子MYO 15 A（c.9611_9612+8delTGGTGAGCAT）变异是一种致病性突变，据我们所知，这种突变还没有在任何数据库中报道。
INTRODUCTION: Autosomal recessive non-syndromic hearing loss (ARNSHL) is a genetically heterogeneous sensorineural disorder with an approximate incidence of 1.4:1000 in neonates. Mutations in more than 60 genes including the MYO15A gene has been reported in patients affected with ARNSHL. In the present study, we report a novel MYO15A mutation identified by clinical exome sequencing and confirmed by Sanger sequencing in a consanguineous Iranian family with ARNSHL.CASE PRESENTATION: A 22-year-old woman with congenital non-syndromic sensorineural hearing loss referred to our medical genetic center. Her parents were consanguineous with F = 1/16 (first cousin), and clinical examination of the patient exclude dysmorphic features. Sanger sequencing of GJB2 and GJB6 genes, which are the most common causes of ARNSHL, was negative. Then she underwent clinical exome sequencing.OUTCOME: We found a novel homozygote variant (c.9611_9612+8delTGGTGAGCAT) in the MYO15A gene which creates a shift in the reading frame starting at codon 3204. This variant was confirmed by Sanger sequencing in the patient and also in her parents who were heterozygous.DISCUSSION: The present results suggest that the homozygous MYO15A (c.9611_9612+8delTGGTGAGCAT) variant is a pathogenic mutation and to the best of our knowledge, this mutation has not been reported in any database.