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

Abstract

Background and ObjectivesAutosomal recessive non-syndromic hearing loss (ARNSHL) with genetic origin is common (1/2000 births). ARNSHL can be associated with mutations in gap junction protein beta 2 (GJB2). To this end, this cohort investigation aimed to find the contribution of GJB2 gene mutations with the genotype-phenotype correlations in 45 ARNSHL cases in the Kurdish population.Subjects and MethodsGenomic DNA was extracted from a total of 45 ARNSHL families. The linkage analysis with 3 short tandem repeat markers linked to GJB2 was performed on 45 ARNSHL families. Only 9 of these families were linked to the DFNB1 locus. All the 45 families who took part were sequenced for confirmation linkage analysis (to perform a large project).ResultsA total of three different mutations were determined. Two of which [c.35delG and c.-23+1G>A (IVS1+1G>A)] were previously reported but (c.299-300delAT) mutation was novel in the Kurdish population. The homozygous pathogenic 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 observed in 4/45 families (8.8%). The degree of hearing loss (HL) in patients with other mutations was less severe than patients with c.35delG homozygous mutation (p<0.001).ConclusionsOur data suggest that GJB2 mutations constitute 20% of the etiology of ARNSHL in Iran; 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 this population.

Identification and clinical implications of a novel pathogenic variant in the <i>GJB2</i> gene causes autosomal recessive non-syndromic hearing loss in a consanguineous Iranian family

“…Various genes causing autosomal recessive nonsyndromic hearing loss (ARNSHL) has been identified from Iran; but mutations related to the GJB2 gene have been reported more frequently (17)(18)(19). Here, a novel homozygous variant identified by Sanger sequencing is reported within an Iranian family.…”

&lt;i&gt;GJB2&lt;/i&gt; Gene Related Nonsyndromic Hearing Loss in Mazandaran Province, North of Iran

“…This mutation is the third most common GJB2 mutation in Czech [39] and also it is reported 4.33% with total allele frequency in Turkish population [41] [42]. In Open Journal of Genetics Iran, the IVS1 + 1G > A is one of five most prevalent GJB2 mutations with frequency about 4.5% [23], with as high as 9.1%in Kurdish ethnic group [14] [43].…”

Screening of 10 DFNB Loci Causing Autosomal Recessive Non-Syndromic Hearing Loss in Two Iranian Populations Negative for GJB2 Mutations

“…Variants in the GJB2 (NM_004004.5) could explain the etiology of ARNSHL in 4% to 35% of patients from different origin, suggesting that GJB2 gene mutations account for a part of ARNSHL in Iran. (4, 5). On the other hand, Iran is a large country with many ethnic groups and high rate of the consanguineous marriages (38.6% on average) (6).…”