Non-Syndromic Autosomal Recessive Deafness in Gaza Strip: A Study of Five GJB2 Gene Mutations

Abstract

Hearing loss is a common, pan-ethnic and highly heterogeneous sensory disorder with an incidence of around 1 in 1000 infants. Genetic causes are thought to be responsible for more than 60% of the cases with the majority of non-syndromic hearing impairment being inherited in an autosomal recessive pattern. The gene that is most frequently mutated in autosomal recessive non-syndromic hearing loss (ARNSHL) is gap junction protein beta-2 (GJB2) which codes for connexin 26 (Cx26). Cx26 plays a key role in potassium homeostasis, which is essential for sound transduction. The aim of this study was to determine the common GJB2 gene mutations in 70 patients suffering from ARNSHL in Gaza strip. The patients were screened for five GJB2 gene mutations namely, c.35delG, c.167delT, c.-23+1G>A, c.229T>C (p.Trp77Arg) and c.235delC. Study results revealed that GJB2 mutations account for at least 35.7% of the ARNSHL with mutant allele frequency of 0.4%. The most frequently encountered mutation was c.35delG which accounted for 35.7% of the ARNSHL cases in either homozygous (34.3%) or heterozygous (1.4%) form and represented about 80.5% of all the detected mutations. The second most frequent mutation was c.235delC which was found only in heterozygous form. The third mutation was c.-23+1G>A which was identified in only one subject (1.4%) in a compound heterozygous form along with c.35delG. The c.167delT and p.Trp77Arg mutations were not observed in our patients. We conclude that there is a significant contribution of GJB2 mutations to congenital ARNSHL in the Palestinian population of Gaza strip. Screening for GJB2 mutations particularly, c.35delG, c.235delC and c.-23+1G>A should be offered to ARNSHL patients to confirm diagnosis of their congenital deafness, to deliver proper genetic counseling for the affected individuals and their families and to help them benefit from prenatal and pre-implantation genetic diagnosis.