Screening of DFNB۳ in Iranian families with autosomal recessive non-syndromic hearing loss reveals a novel pathogenic mutation in the MyTh۴ domain of the MYO۱۵A gene in a linked family

Objective(s): Non-syndromic sensorineural hearing loss (NSHL) is a common disorder affecting approximately ۱ in ۵۰۰ newborns. This type of hearing loss is extremely heterogeneous and includes over ۱۰۰ loci. Mutations in the GJB۲ gene have been implicated in about half of autosomal recessive NSHL (ARNSHL) cases, making this the most common cause of ARNSHL. For the latter form of deafness, most frequent genes proposed include GJB۲, SLC۲۶A۴, MYO۱۵A, OTOF, and CDH۲۳ worldwide. Materials and Methods: the aim of the present study was to determine the role of MYO۱۵A gene mutations in Iranian families. Thirty Iranian families with over three deaf children and negative for GJB۲ using genetic linkage analysis (GLA), followed by mutation screening by DNA sequencing were enrolled. Results: One family (۳.۳۳%) showed linkage to DFNB۳ and a novel mutation was identified in the MYO۱۵A gene (c.۶۴۴۲T>A) as the disease-causing mutation. Mutation co-segregated with hearing loss in the family but was not present in the ۱۰۰ ethnicity-matched controls. Conclusion: Our results confirmed that the hearing loss of the linked Iranian family was caused by a novel missense mutation in the MYO۱۵A gene. This mutation is the first to be reported in the world and affects the first MyTH۴ domain of the protein.

Keywords:

Hearing Loss , Iran , Linkage analysis , MYO۱۵A , Mutation