Identification of novel gene variants causing autosomal recessive non-syndromic hearing loss in Iranian families

Author:

Ajam-Hosseini Mobarakeh1,Parvini Farshid2,Angaji Abdolhamid1

Affiliation:

1. Kharazmi University

2. Semnan University

Abstract

Abstract

Background Hearing loss (HL) is known as the most common sensory disorder in humans, with an incidence in 466 million people worldwide. This disorder is genetically highly heterogeneous, so that among the 180 genes responsible for HL, a disproportionate share of genes is involved in different ethnicities. Here, we report the underlying genetic cause of non-syndromic hearing loss (NSHL) segregating in four Iranian unrelated families. Methods In the first step, patients were examined for mutations in the common genes GJB2 and GJB6. After confirming the negativity of mutations in these genes, the affected patients were subjected to targeted exome sequencing (TES). Subsequently, Sanger sequencing was used to confirm the mutations found in the patients and their family members. In silico analyses were used to consider the possible deleterious effect of the identified variants on encoded proteins. Results TES revealed a novel intronic mutation c.490-8C > A in CABP2 gene, a novel ~ 154 kb deletion mutation including OTOA gene involved in HL, and two previously reported mutations c.413C > A and c.966dupC in TMPRSS3 and COL11A2 genes, respectively. In addition, segregation analysis and in-silico evaluations confirmed the disease-causing nature of mutations found. Conclusion Our findings could extend the pathogenic mutations spectrum of NSHL, highlight the high genetic heterogeneity of HL and also aid to conduct genetic counseling, prenatal diagnosis and clinical management of HL in the Iranian population.

Publisher

Research Square Platform LLC

Reference50 articles.

1. Novel Mutations in KCNQ4, LHFPL5 and COCH Genes in Iranian Families with Hearing Impairment;Mehregan H,2019

2. Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss;Trpchevska N;Am J Hum Genet,2022

3. Kalra G. Multi-Omic Analysis of Hearing Difficulty Risk Loci and Gene Regulatory Networks in the Mammalian Cochlea. Doctoral Dissertation, University of Maryland, Baltimore. 2021.

4. Study of genes and mutations spectrum causing non-syndromic hearing loss in Iran: A review study;Ajam-Hossieni M;KAUMS J (FEYZ),2022

5. Identification of novel variants in Iranian consanguineous pedigrees with nonsyndromic hearing loss by next-generation sequencing;Bitarafan F;J Clin Lab Anal,2020

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