Koohiyan Mahbobeh, Hashemzadeh-Chaleshtori Morteza, Salehi Mansoor, Abtahi Hamidreza, Reiisi Somayeh, Pourreza Mohammad Reza, Noori-Daloii Mohammad Reza, Tabatabaiefar Mohammad Amin
Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Cellular and Molecular Research Center, Basic Health Research Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Int J Pediatr Otorhinolaryngol. 2018 Apr;107:121-126. doi: 10.1016/j.ijporl.2018.01.012. Epub 2018 Jan 31.
Hereditary hearing loss (HL) is a noticeable concern in medicine all over the world. On average, 1 in 166 babies born are diagnosed with HL in Iran, which makes it a major public health issue. Autosomal recessive non-syndromic HL (ARNSHL) is the most prevalent form of HL. Although over 60 genes have been identified for ARNSHL, GJB2 mutations are the most prevalent causes of ARNSHL in many populations. Previous studies have estimated the average frequency of GJB2 mutations to be between 16 and 18% in Iran, but would vary among different ethnic groups. In the present study, we aimed to determine the frequency and mutation profile of 70 deaf patients from two different provinces (center and west) of Iran.
We enrolled 70 Iranian deaf patients with ARNSHL from Isfahan (40 family) and Hamedan (30 family) provinces. After extraction of genomic DNA, the entire coding region of GJB2 was directly sequenced in all patients. Multiplex PCR was used for detection of del(GJB6-D13S1830) and del(GJB6-D13S1854) in the GJB6 gene. In silico analyses were also performed by available software tools.
A total of eleven different mutations were detected, nine of which were previously reported and the other two (c.130T > G and c.178T > G) were novel. Homozygous GJB2 mutations were observed in 22.5% and 20% of all the subjects from Isfahan and Hamedan provinces, respectively. c.35delG was the most frequent mutation. One compound heterozygous genotype (c.358_360delGAG/c.35delG) was observed for c.35delG. Screening for the two GJB6 deletions did not reveal any positive sample among heterozygous or GJB2 negative samples.
The present study suggests that mutations in the GJB2 gene specially c.35delG are important causes of ARNSHL in the center and west of Iran. Totally, 15% of the patients were heterozygous carriers. Further investigation is needed to detect the genetic cause of HL in the patients with monoallelic GJB2 mutations.
遗传性听力损失（HL）是全球医学界关注的一个重要问题。在伊朗，平均每166名新生儿中就有1名被诊断患有HL，这使其成为一个重大的公共卫生问题。常染色体隐性非综合征性HL（ARNSHL）是HL最常见的形式。尽管已经确定了60多个与ARNSHL相关的基因，但在许多人群中，GJB2突变是ARNSHL最常见的病因。先前的研究估计，伊朗GJB2突变的平均频率在16%至18%之间，但不同种族之间会有所差异。在本研究中，我们旨在确定来自伊朗两个不同省份（中部和西部）的70名耳聋患者的突变频率和突变谱。
我们招募了来自伊斯法罕（40个家庭）和哈马丹（30个家庭）省的70名患有ARNSHL的伊朗耳聋患者。提取基因组DNA后，对所有患者的GJB2整个编码区进行直接测序。采用多重PCR检测GJB6基因中的del（GJB6-D13S1830）和del（GJB6-D13S1854）。还使用可用的软件工具进行了计算机分析。
共检测到11种不同的突变，其中9种先前已有报道，另外两种（c.130T＞G和c.178T＞G）是新发现的。在伊斯法罕和哈马丹省的所有受试者中，分别有22.5%和20%观察到纯合GJB2突变。c.35delG是最常见的突变。观察到一种c.35delG的复合杂合基因型（c.358_360delGAG/c.35delG）。对两种GJB6缺失的筛查未在杂合或GJB2阴性样本中发现任何阳性样本。
本研究表明，GJB2基因的突变，特别是c.35delG，是伊朗中部和西部ARNSHL的重要病因。总的来说，15%的患者是杂合携带者。对于单等位基因GJB2突变的患者，需要进一步研究以检测HL的遗传病因。
