Whole Exome Sequencing of Non-Syndromic Hearing Loss Patients

Hearing loss is the second most common disease after mental retardation in Iran.Autosomal recessive non-syndromic hearing loss (ARNSHL) is an extreme and highly heterogeneous disease, for which more than 70 genes have been identified. Considering the frequency of family marriage as well as the im-portance of ARNSHLin Iran, we evaluated the genetic factors involved in this type of deafness.

We performed the whole exome sequencing (WES) of eight Iranian subjects with severe non-syndromic hearing loss selected from 110 well-characterized subjects with non-syndromic hearing loss from 2017-2019.The patients with mutated GJB2and GJB6genes were excluded from the study.

The use of the whole exome sequencing method revealed 10 different mutations in 7 genes, including SLC26A4 (c.1234G>T), FGF3(c.45DelC, c.466T>C), ADGRV1(c.12528-2A>C, c.16226-16227insAGTC), OTOG(c.7454delG), OTOF(c.3570+2T>C), ESPN(c.992G>A), OTOA(c.2359G>T, c.2353A>C). Seven new variants were observed in seven families including SLC26A4 (c.1234G>T), FGF3(c.45DelC), ADGRV1(c.12528-2A>C), OTOG(c.7454delG), ADGRV1(c.16226-16227insAGTC), OTOF(c.3570+2T>C).

The causal mutation of ARNSHLwas found in all patients using the WES. Meta-analysis studies can help to identify common mutations causing deafness in any population to facilitate identification of carriers and subjects with deafness.