Identification of nonsense mutation in TMC1 gene inducing hearing loss by clinical exome sequencing

Hearing loss is one of the most common sensorineural disorders, affecting one in 1000 individuals that can be classified into syndromic and non-syndromic. TMC1 gene has been identified as a non-syndromic gene for both autosomal and recessive forms. In this study, we characterized a UAE consanguineous family with congenital profound non-syndromic hearing loss. By using clinical exome sequencing, Sanger sequencing and PCR-RFLP, we identified the p.Arg34X as the disease-associated variant. The screening of other families with deafness, revealed the presence of this nonsense mutation in one additional family and suggested that p.Arg34X is major contributor to DFNB7/11 form of deafness in UAE population. To the best of our knowledge, this is the first study associating TMC1 mutations to hearing loss in the GCC region.