| الوصف: |
Hearing loss (HL) is a common and highly heterogeneous sensory disorder which affects approximately 1 in1000 infants. Genetic causes are thought to be responsible for more than 60% of the cases with the majority of non-syndromic HL being inherited in an autosomal recessive pattern. The gene first identified in 1997 to be associated with non syndromic autosomal recessive deafness (NSARD) was Gap junction beta 2 (GJB2) which codes for Connexin 26 (Cx26). Gap junction protein belongs to a family of transmembrane proteins with about 20 members in humans. Cx26, has been shown to play a key role in potassium homeostasis, which is essential for sound transduction. The aim of this study was to study the mutations in Cx26 gene in families with NSARD in Gaza strip. Descriptive analytical design was used to conduct this study and samples selected from three HL institutions in Gaza strip. The patients were screened for five GJB2 gene mutations namely, 35delG, 167delT, IVS1+1G>A, W77R and 235delC. First, the 35delG and 167delT mutations were screened using restriction enzyme analysis of the corresponding PCR products. Second, when no 35delG or 167delT mutations was detected, screening was continued for the IVS1+1G>A, 235delC and W77R mutations. Our results revealed that GJB2 mutations contributed to 44.3% of the NSARD with allele frequency of 0.4%. The mutations were identified in either heterozygous or homozygous form. The most frequently encountered mutation was 35delG which accounted for 35.7% of the NSARD in either heterozygous (1.4%) or homozygous (34.3%) and represented about 80.5% of all mutations detected in this study. The second detected mutation was 235delC which accounted for 8.6% of NSARD and was recorded in only heterozygous form. The third mutation was IVS1+1G>A which was identified in only one proband (1.4%) in a compound heterozygous form along with 35delG, Whereas, 167delT and W77R were not observed in our samples. We concluded that there is a significant contribution of GJB2 mutations to congenital NSARD in the Palestinian population of Gaza strip. Screening for GJB2 mutations particularly, 35delG, 235delC and IVS1+1G>A should be offered to NSARD patients to confirm diagnosis of their congenital deafness, to deliver proper genetic counseling for the affected individuals and their families and to provide the patients the optimal management. |