Hussain Shahid, Khattak Jabar Zaman, Ismail Mohammad, Mansoor Qaisar, Khan Mohammad Haroon
Department of Bioinformatics and Biosciences, Capital University of Science and Technology, Islamabad, Pakistan.
Department of Bioinformatics and Biotechnology, International Islamic University Islamabad, Pakistan.
Pak J Pharm Sci. 2018 Jan;31(1):51-56.
Deafness is the most common sensory disorder, which affects 1/1000 neonates globally. Genetic factors are major contributors for hearing impairment. This study was conducted to explore the linkage of DFNB loci and their mutations with NSHL in selected Pakistani families. We included 10 families with history of deafness from district Mardan, Pakistan. Blood sample (5ml) along with personal and clinical information was collected from the available family members including both diseased and un-affected individuals. Genomic DNA was amplified using loci specific STR markers to investigate the linkage of DFNB loci. Family found linked with DFNB4 locus was screened for SLC26A4 mutations. One out of the ten explored families was found linked with DFNB4 locus which was further investigated for SLC26A4 gene mutation through direct DNA sequencing. Two novel mutations were observed in the studied family, one at splice donor site (164+2T>G) and the other at position 164+5C>G only in the affected members of the linked family. DFNB4 locus was found linked in the present study which harbors SLC26A4 gene. The novel mutation of SLC26A4 gene at the splice donor site results in skipping of the first coding exon and thus can lead to loss of expression of SLC26A4 product in the inner ear.
耳聋是最常见的感觉障碍，全球每1000名新生儿中就有1人受其影响。遗传因素是听力障碍的主要成因。本研究旨在探讨巴基斯坦特定家庭中DFNB位点及其突变与非综合征性听力损失（NSHL）之间的联系。我们纳入了来自巴基斯坦马尔丹地区有耳聋病史的10个家庭。从包括患病和未患病个体在内的现有家庭成员中采集了5毫升血液样本以及个人和临床信息。使用位点特异性STR标记扩增基因组DNA，以研究DFNB位点的连锁关系。对与DFNB4位点连锁的家庭进行SLC26A4突变筛查。在10个被研究的家庭中，有1个家庭与DFNB4位点连锁，通过直接DNA测序对其SLC26A4基因突变进行了进一步研究。在该研究家庭中观察到两个新突变，一个在剪接供体位点（164 + 2T>G），另一个仅在连锁家庭的患病成员中位于164 + 5C>G位置。在本研究中发现DFNB4位点与携带SLC26A4基因的区域连锁。SLC26A4基因在剪接供体位点的新突变导致第一个编码外显子缺失，从而可能导致内耳中SLC26A4产物表达缺失。
