Koohiyan Mahbobeh, Noori-Daloii Mohammad Reza, Hashemzadeh-Chaleshtori Morteza, Salehi Mansoor, Abtahi Hamidreza, Tabatabaiefar Mohammad Amin
Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Cancer Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Audiol Neurootol. 2019;24(5):258-263. doi: 10.1159/000502251. Epub 2019 Oct 29.
Hereditary hearing loss (HL) can originate from mutations in one of many genes involved in the complex process of hearing. CABP2 mutations have been reported to cause moderate HL. Here, we report the whole exome sequencing (WES) of a proband presenting with prelingual, severe HL in an Iranian family.
A comprehensive family history was obtained, and clinical evaluations and pedigree analysis were performed in the family with 2 affected members. After excluding mutations in the GJB2 gene and 7 other most common autosomal recessive nonsyndromic HL (ARNSHL) genes via Sanger sequencing and genetic linkage analysis in the family, WES was utilized to find the possible etiology of the disease.
WES results showed a novel rare variant (c.311G>A) in the CABP2gene.This missense variant in the exon 4 of the CABP2gene meets the criteria of being pathogenic according to the American College of Medical Genetics and Genomics (ACMG) interpretation guidelines.
Up to now, 3 mutations have been reported for the CABP2gene to cause moderate ARNSHL in different populations. Our results show that CABP2variantsalso cause severe ARNSHL, adding CABP2to the growing list of genes that exhibit phenotypic heterogeneity. Expanding our understanding of the mutational spectrum of HL genes is an important step in providing the correct clinical molecular interpretation and diagnosis for patients.
遗传性听力损失（HL）可源于参与听力复杂过程的众多基因中的一个发生突变。据报道，CABP2基因突变可导致中度HL。在此，我们报告了一个伊朗家庭中一名患有语前重度HL的先证者的全外显子组测序（WES）结果。
获取了详尽的家族病史，并对这个有2名受影响成员的家庭进行了临床评估和系谱分析。在通过桑格测序和家族中的遗传连锁分析排除了GJB2基因及其他7个最常见的常染色体隐性非综合征性HL（ARNSHL）基因中的突变后，利用WES来寻找该疾病可能的病因。
WES结果显示CABP2基因存在一种新的罕见变异（c.311G>A）。根据美国医学遗传学与基因组学学会（ACMG）的解读指南，CABP2基因第4外显子中的这种错义变异符合致病标准。
到目前为止，已有报道称CABP2基因的3种突变在不同人群中导致中度ARNSHL。我们的结果表明，CABP2变异也可导致重度ARNSHL，这使得CABP2加入到了表现出表型异质性的基因名单中。扩展我们对HL基因突变谱的认识是为患者提供正确的临床分子解读和诊断的重要一步。
