Targeted sequencing of CDH23 and GJB2 genes in an Iranian pedigree with Usher syndrome and non-syndromic hearing loss

Hearing loss is genetically classified as non-syndromic and syndromic deafness. Mutations in the GJB2 gene are the most main reason for autosomal recessive non-syndromic hearing loss. Moreover, Usher syndrome is the most common type of syndromic hearing and vision loss. Three types of this syndrome can be distinguished based on the hearing and vision deficit severity. Usher type 1 is the most severe type, defined by congenital bilateral profound hearing loss, vestibular areflexia and retinitis pigmentosa. Here, we present detailed analyses of clinical and genetical characteristics of two distinct families with both Usher syndrome and non-syndromic hearing loss in a pedigree. The Sanger sequencing analysis of the GJB2 gene revealed a homozygous c.35delG (p.Gly12Valfs *2) nonsense mutation in two cases with non-syndromic hearing loss. In addition, targeted exome sequencing of hearing loss-related genes identified a homozygous c.2206C > T (p.Arg736Ter) variant in CDH23 gene concerning two affected brothers with Usher syndrome type 1. The current investigation described the disease-causing variant in the CDH23 with new transferring form and implied the critical role of molecular testing in precise clinical diagnosis, genetic counselling of congenital hearing loss.