Investigating Seven Recently Identified Genes in ۱۰۰ Iranian Families with Autosomal Recessive Non-syndromic Hearing Loss

Objectives: Hearing loss (HL) is the most common sensory disorder, and affects ۱ in ۱۰۰۰ newborns. About ۵۰% of HL is due to genetics and ۷۰% of them are non-syndromic with a recessive pattern of inheritance. Up to now, more than ۵۰ genes have been detected which are responsible for autosomal recessive non-syndromic hearing loss, (ARNSHL). In  Iran, HL is one of the most common disabilities due to consanguineous marriages. The aim was to investigate the prevalence of three new ARHL genes (GJB۴, GJC۳, and SLITRK۶) reported in neighboring countries among Iranian families with ARNSHL. Methods: One hundred unrelated families with at least two affected siblings in consanguineous marriage, who were negative for GJB۲ gene mutations, were selected. By using three STR markers for each gene, homozygosity mapping was performed. Results: Two families showed linkage to GJB۴, six families were linked to GJC۳ and only one family linked to SLITRK۶. The samples of these families who showed linkage were sent for Sanger sequencing to detect the causative mutations. However, after analyzing the sequencing results, no mutation could be detected in either of the families. Molecular analysis for these nine families is underway in order to determine the pathogenic mutations using whole exome sequencing. Discussion: These data demonstrate a very low prevalence of mutation in these three genes (GJB۴, GJC۳, and SLITRK۶) in the Iranian population, since no mutation was detected in our study group of ۱۰۰ families.

Keywords:

Autosomal recessive non-syndromic hearing loss , Homozygosity mapping , Linkage analysis , Iran