Identification of GJB2 Variants in 75 Unrelated Iranian Autosomal Recessive Non-syndromic Hearing Loss Patients

Hearing loss (HL) is the most prevalent sensory disease in humans. HL is among the most clinically and genetically heterogeneous disorders. Pathogenic variants in GJB2 are the principal cause of HL in many populations. Therefore, GJB2 analysis should be considered as the first step for HL.

This study aimed to find causative variants in the GJB2 gene in 75 unrelated Iranian patients who suffered from Autosomal recessive non-syndromic hearing loss (ARNSHL).

Peripheral blood samples were used for genomic DNA extraction. PCR-direct sequencing was performed to detect GJB2 mutations.

In this study, thirty-four chromosomes (21.33%) carried GJB2 mutations. In general, 10 variants were detected among 19 patients. Seven cases were homozygous for c.35delG; (p.Gly12Valfs*2), two were homozygous for c.71G>A; (p.Trp24*), two were homozygous for c.358-360delGAG (p.Glu120del), and two were homozygous for c.-23+1G>A mutation. One patient was a compound heterozygote for c.35delG and c.-23+1G>A mutations, and another patient with compound heterozygosity for c.290dupA and c.235delC mutations were determined. Four patients carried a mono-allelic variant in the GJB2 including c.126G>T; (p.Glu42Asp), c.23C>T; (p.Thr8Met), c.445G>A; (p.Ala149Thr) and c.269T>C; (p.Leu90Pro). Accordingly, c.35delG mutation was the most common variant in this study.

Finding common variants of HL mutations in different populations can elevate the diagnostic value of molecular testing in the screening of affected individuals, and can improve counselling to minimize the risk of having affected offspring for at-risk couples. Besides, early diagnosis can easily lead to speech development and prevents further problems.