Kashef Atie, Nikzat Nooshin, Bazzazadegan Niloofar, Fattahi Zohreh, Sabbagh-Kermani Farahnaz, Taghdiri Maryam, Azadeh Batool, Mojahedi Faezeh, Khoshaeen Atefeh, Habibi Haleh, Najmabadi Hossein, Kahrizi Kimia
Genetic Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran; Deputy of Student Research, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Genetic Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Int J Pediatr Otorhinolaryngol. 2015 Feb;79(2):136-8. doi: 10.1016/j.ijporl.2014.11.024. Epub 2014 Dec 3.
Hereditary hearing loss is the most common neurosensory disorder in humans. Half of the cases have genetic etiology with extraordinary genetic heterogeneity. Mutations in one gene, GJB2, are the most common cause for autosomal recessive non-syndromic hearing loss (ARNSHL) in many different populations. GJB2 encodes a gap junction channel protein (connexin 26), and is located on DFNB1 locus on chromosome 13q12.11 which also involve another connexin gene, GJB6. Mutation screening of GJB2 revealed that a high number of patients with deaf phenotype have heterozygous genotype and carry only one mutant allele. As the first comprehensive study in Iran, we have targeted GJB2-related Iranian heterozygotes, looking for second mutant allele which leads to hearing impairment. They bear first mutation in their coding exon of GJB2.
Using PCR-based direct sequencing, we assessed 103 patients with ARNSHL for variants in non-coding exon and promoter region of this gene, for the first time in Iran.
We have identified the second mutant allele in splice site of exon-1 of GJB2 which is known as IVS1+1G>A in 17 probands. We found no mutation in promoter region of GJB2.
Our findings reveal that IVS1+1G>A mutation in noncoding exon of GJB2 is the most common mutation after 35delG within multi ethnical Iranian heterozygote samples. It emphasizes to approach exon1 of GJB2 in case of ARNSHL genetic diagnosis.
遗传性听力损失是人类最常见的神经感觉障碍。半数病例具有遗传病因，且遗传异质性极高。在许多不同人群中，一个基因GJB2的突变是常染色体隐性非综合征性听力损失（ARNSHL）最常见的病因。GJB2编码一种间隙连接通道蛋白（连接蛋白26），位于13号染色体13q12.11的DFNB1位点上，该位点还涉及另一个连接蛋白基因GJB6。对GJB2的突变筛查显示，大量有耳聋表型的患者具有杂合基因型，仅携带一个突变等位基因。作为伊朗的第一项综合性研究，我们针对与GJB2相关的伊朗杂合子，寻找导致听力障碍的第二个突变等位基因。他们在GJB2的编码外显子中携带第一个突变。
在伊朗首次使用基于聚合酶链反应（PCR）的直接测序法，评估103例ARNSHL患者该基因非编码外显子和启动子区域的变异情况。
我们在17名先证者中，于GJB2外显子1的剪接位点发现了第二个突变等位基因，即众所周知的IVS1+1G>A。我们在GJB2的启动子区域未发现突变。
我们的研究结果显示，在多民族的伊朗杂合子样本中，GJB2非编码外显子中的IVS1+1G>A突变是继35delG之后最常见的突变。这强调了在进行ARNSHL基因诊断时应对GJB2的外显子1进行检测。
