J Audiol Otol.  2019 Jan;23(1):20-26. 10.7874/jao.2018.00185.

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

Affiliations
  • 1Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran. mchalesh@yahoo.com
  • 2Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
  • 3Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
  • 4Kurdistan Provinces Social Welfare Organization, Kurdistan, Iran.
  • 5Department of Genetics, Falavarjan Branch, Islamic Azad University, Isfahan, Iran.
  • 6Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

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 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 METHODS
Genomic 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).
RESULTS
A 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).
CONCLUSIONS
Our 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.

Keyword

Hearing loss; Autosomal recessive non-syndromic hearing loss; Gap junction protein beta 2

MeSH Terms

Cohort Studies
Connexins
DNA
Genetic Association Studies
Genotype
Hearing Loss*
Hearing*
Humans
Iran*
Microsatellite Repeats
Connexins
DNA
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