title: Screening of DFNB3 in Iranian families with autosomal recessive non-syndromic hearing loss reveals a novel pathogenic mutation in the MyTh4 domain of the MYO15A gene in a linked family.
abstract: OBJECTIVE
  Non-syndromic sensorineural hearing loss (NSHL) is a common disorder affecting approximately 1 in 500 newborns. This type of hearing loss is extremely heterogeneous and includes over 100 loci. Mutations in the GJB2 gene have been implicated in about half of autosomal recessive non-syndromic hearing loss (ARNSHL) cases, making this the most common cause of ARNSHL. For the latter form of deafness, most frequent genes proposed include GJB2, SLC26A4, MYO15A, OTOF, and CDH23 worldwide.
  
  
  METHODS
  The aim of the present study was to define the role and frequency of MYO15A gene mutation in Iranian families. In this study 30 Iranian families were enrolled with over three deaf children and negative for GJB2. Then linkage analysis was performed by six DFNB3 short tandem repeat markers. Following that, mutation detection accomplished using DNA sequencing.
  
  
  RESULTS
  One family (3.33%) showed linkage to DFNB3 and a novel mutation was identified in the MYO15A gene (c.6442T>A): as the disease-causing mutation. Mutation co-segregated with hearing loss in the family but was not present in the 100 ethnicity-matched controls.
  
  
  CONCLUSIONS
  Our results confirmed that the hearing loss of the linked Iranian family was caused by a novel missense mutation in the MYO15A gene. This mutation is the first to be reported in the world and affects the first MyTH4 domain of the protein.
authors.affiliation: Department of Genetics, Faculty of Basic Sciences, University of Shahrekord, Shahrekord, Iran.
authors.forename: Somayeh
authors.initials: S
authors.lastname: Reiisi
authors.affiliation: Medical Genetics Dept., Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Mohammad Amin
authors.initials: MA
authors.lastname: Tabatabaiefar
authors.affiliation: Medical Genetics Dept., National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
authors.forename: Mohammad Hosein
authors.initials: MH
authors.lastname: Sanati
authors.affiliation: Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran.
authors.forename: Morteza Hashemzadeh
authors.initials: MH
authors.lastname: Chaleshtori
keywords: Hearing loss; Iran; Linkage analysis; MYO15A; mutation