Frequency of Connexin26 Gene Mutations in Autosomal Recessive Non-syndromic Deafness in Kermanshah(2002-4)

Introduction: Hearing loss is the most common sensory defect in humans, affecting approximately 1 in 1000 neonates in which genetic factors are involved in more than 50%. Connexin 26 or GJB2 gene mutations are responsible for half of autosomal recessive non-syndromic hearing losses. The purpose of this study was to determine the GJB2 mutations frequency in autosomal recessive non-syndromic deafness in Kermanshah.

Materials & Methods: Among families with hearing loss referring to Genetics Counseling Centers of Kermanhah Welfare Organization, seventy seven families met inclusion criteria for autosomal recessive non-syndromic hearing loss to screen for GJB2 mutations. At first 35delG homozygous samples determined by Allele-Specific PCR were excluded from the study and additional testing was not done. DHPLC analysis of the coding sequence of GJB2 was completed and complemented by direct sequencing in case abnormal elution profiles were observed. Finally, mutations frequencies based on numbers of individuals and chromosomes were calculated.

Results: In this study frequency of individuals with 35delG mutation was 14.28 %( 11 of 77 families). Our work showed 23.38% GJB2 mutation rate in deaf samples. In other words, 154 chromosomes were analyzed; Twenty nine chromosomes (18.83%) had a mutation in GJB2 gene. The 35delG frequency was 58.62% among other mutations. The frequency of the 35delG mutation decreases from west to east in Kermanshah Province. After the 35delG mutation, other common mutations were R32H, delE120, IVS1+1G>A. The rate of mutation in exon 1 was 10.34% of allelic mutations in this population. While this mutation is relatively uncommon in other series and has not been previously identified in Iran.  

Conclusion: On the basis of this investigation, connexin26 gene-related deafness frequency is approximately 23% suggesting that other genes may be involved in hearing loss in Kermanshah Province and further studies are needed to find out these genes. So screening these mutations (35delG, R32H, delE120, IVS1+1G>A) for deaf individuals referring to Genetics Counseling Centers before marriage and or pregnancy is recommended.