Determination of GJB2 gene mutations in the autosomal recessive non-syndromic hearing lost individuals with SSCP and DNA sequencing analysis

Mutations in connexin 26 gene (GJB2) lead to significant proportion of non- syndromic autosomal recessive congenital hearing loss in all populations studied so far. The 35delG mutation is the most common GJB2 mutation in white populations. To determine the percentage of hearing loss attributed to connexin 26 gene and the types of mutations in Turkish population, unrelated 96 patients with autosomal recessive non-syndromic congenital deafness were screened. The 35delG mutations were detected with competitive amplification refractory mutation system (C-ARMS) that we developed. The other GJB2 mutations were screened with single strand conformation polymorphism (SSCP) and silver sequencing analysis. Six different types of mutations were found in 28 of the patients with severe to profound hearing loss. Mutation 35delG was the most common, accounting for 76.8% of all GJB2 deafness alleles. Three non-35delG mutations (W24X, 310dell4 and delE120) were identified more than once with relative frequencies of 10.7%, 5.4%, and 3.6%, respectively. Two novel missense mutations (P173S and Q80K) compound heterozygous with 35delG mutation also were observed. Our results indicate that connexin 26 mutations are the cause in 29% of Turkish patients with autosomal recessive non-syndromic congenital hearing loss. Key Words: Non syndromic hearing loss, GJB2, DFNB1, Connexin 26, 35delG