Shaikh Hina, Waryah Ali M, Narsani Ashok K, Iqbal Muhammad, Shahzad Mohsin, Waryah Yar M, Shaikh Naila, Mahmood Amber
Molecular Biology and Genetics Department, Medical Research Center, Liaquat University of Medical and Health Sciences, Jamshoro, Pakistan.
Institute of Ophthalmology, Liaquat University of Medical and Health Sciences, Jamshoro, Pakistan.
Biochem Genet. 2017 Dec;55(5-6):410-420. doi: 10.1007/s10528-017-9828-3. Epub 2017 Oct 31.
CIB2 and GJB2 genes variants contribute significantly in familial cases of prelingual recessive hearing loss (HL). This study was aimed to determine the CIB2 and GJB2 variants and associated phenotype in 150 non-familial individuals with HL. After getting informed consent, 150 non-familial deaf patients were enrolled and blood samples were obtained for DNA extraction. Pure tone air conduction audiometry was performed. Coding exons of CIB2 and GJB2 genes were Sanger sequenced. A tetra primer ARMS assay was developed for recurrent CIB2 variant. Four bi-allelic GJB2 variants, c.71G>A p.(Trp24*), c.231G>A p.(Trp77*), c.235delC p.(Leu79Cysfs3*) and c.35delG p.(Gly11Leufs24*), were found in nine hearing impaired individuals. We also found four homozygotes and five carriers of c.380G>A p. (Arg127His) variant of controversial clinical significance. CIB2 sequencing revealed single recurrent variant c.272T>C p. (Phe91Ser) segregating with HL in ten individuals. Among our patients, c.71G>A (p.Trp24*) was the most common variant, accounted for 45% of GJB2 variants. Two known GJB2 variants, c.235delC p. (Leu79Cysfs3*) and c.310del14 p. (Lys105Argfs2*), are reported here for the first time in Pakistani population. Our data further support the benign nature of c.380G>A p. (Arg127His) variant. For CIB2, c.272T>C p. (Phe91Ser) is the second common cause of HL among our sporadic cases. Phenotypically, in our patients, individuals homozygous for GJB2 variants had profound HL, whereas CIB2 homozygotes had severe to profound prelingual HL. Our results suggest that GJB2 and CIB2 are common cause of HL in different Pakistani ethnicities.
CIB2和GJB2基因变异在家族性语前隐性听力损失（HL）病例中起重要作用。本研究旨在确定150例非家族性HL患者的CIB2和GJB2变异及相关表型。在获得知情同意后，招募了150例非家族性耳聋患者，并采集血样进行DNA提取。进行了纯音气导听力测定。对CIB2和GJB2基因的编码外显子进行了桑格测序。针对复发性CIB2变异开发了一种四引物扩增阻滞突变系统（ARMS）检测方法。在9例听力受损个体中发现了4种双等位基因GJB2变异，即c.71G>A p.(Trp24*)、c.231G>A p.(Trp77*)、c.235delC p.(Leu79Cysfs3*)和c.35delG p.(Gly11Leufs24*)。我们还发现了4例c.380G>A p.(Arg127His)变异的纯合子和5例携带者，该变异的临床意义存在争议。CIB2测序显示，在10例个体中，单一复发性变异c.272T>C p.(Phe91Ser)与HL共分离。在我们的患者中，c.71G>A (p.Trp24*)是最常见的变异，占GJB2变异的45%。两种已知的GJB2变异，即c.235delC p.(Leu79Cysfs3*)和c.310del14 p.(Lys105Argfs2*)，首次在巴基斯坦人群中报道。我们的数据进一步支持了c.380G>A p.(Arg127His)变异的良性性质。对于CIB2，c.272T>C p.(Phe91Ser)是我们散发病例中HL的第二大常见病因。在表型上，在我们的患者中，GJB2变异的纯合子个体患有重度HL，而CIB2纯合子个体患有重度至极重度语前HL。我们的结果表明，GJB2和CIB2是不同巴基斯坦族群中HL的常见病因。
