Mutations in GJB2 as Major Causes of Autosomal Recessive Non-Syndromic Hearing Loss: First Report of c.299-300delAT Mutation in Kurdish Population of Iran
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Background and Objectives: Autosomal recessive non-syndromic hearing loss (ARNSHL)with genetic origin is common (1/2000 births). ARNSHL can be associated with mutations ingap junction protein beta 2 (GJB2). To this end, this cohort investigation aimed to find thecontribution of GJB2 gene mutations with the genotype-phenotype correlations in 45 ARNSHLcases in the Kurdish population. Subjects and Methods: Genomic DNA was extractedfrom a total of 45 ARNSHL families. The linkage analysis with 3 short tandem repeat markerslinked to GJB2 was performed on 45 ARNSHL families. Only 9 of these families werelinked to the DFNB1 locus. All the 45 families who took part were sequenced for confirmationlinkage analysis (to perform a large project). Results: A total of three different mutationswere determined. Two of which [c.35delG and c.-23+1G>A (IVS1+1G>A)] were previouslyreported but (c.299-300delAT) mutation was novel in the Kurdish population. The homozygouspathogenic mutations of GJB2 gene was observed in nine out of the 45 families(20%), also heterozygous genotype (c.35delG/N)+(c.-23+1G>A/c.-23+1G>A) were observedin 4/45 families (8.8%). The degree of hearing loss (HL) in patients with other mutationswas less severe than patients with c.35delG homozygous mutation (p<0.001). Conclusions:Our data suggest that GJB2 mutations constitute 20% of the etiology of ARNSHL inIran; moreover, the c.35delG mutation is the most common HL cause in the Kurdish population. Therefore, these mutations should be included in the molecular testing of HL in thispopulation.
Abstract
Background and Objectives: Autosomal recessive non-syndromic hearing loss (ARNSHL)with genetic origin is common (1/2000 births). ARNSHL can be associated with mutations ingap junction protein beta 2 (GJB2). To this end, this cohort investigation aimed to find thecontribution of GJB2 gene mutations with the genotype-phenotype correlations in 45 ARNSHLcases in the Kurdish population. Subjects and Methods: Genomic DNA was extractedfrom a total of 45 ARNSHL families. The linkage analysis with 3 short tandem repeat markerslinked to GJB2 was performed on 45 ARNSHL families. Only 9 of these families werelinked to the DFNB1 locus. All the 45 families who took part were sequenced for confirmationlinkage analysis (to perform a large project). Results: A total of three different mutationswere determined. Two of which [c.35delG and c.-23+1G>A (IVS1+1G>A)] were previouslyreported but (c.299-300delAT) mutation was novel in the Kurdish population. The homozygouspathogenic mutations of GJB2 gene was observed in nine out of the 45 families(20%), also heterozygous genotype (c.35delG/N)+(c.-23+1G>A/c.-23+1G>A) were observedin 4/45 families (8.8%). The degree of hearing loss (HL) in patients with other mutationswas less severe than patients with c.35delG homozygous mutation (p<0.001). Conclusions:Our data suggest that GJB2 mutations constitute 20% of the etiology of ARNSHL inIran; moreover, the c.35delG mutation is the most common HL cause in the Kurdish population. Therefore, these mutations should be included in the molecular testing of HL in thispopulation.
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