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

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.