Mutational analyses of the hereditary and non-syndromic hearing loss cases in candidate loci

Mutations of Cx-26 gene, which is coding the subunit of conexon gap junction protein, is primarily responsible for non-syndromic, sensorineural hearing loss. The incidence of it has been reported to be more than 1/1000 in various populations. Especially, 35delG mutation in the second exon of this gene frequency is over 70% among individuals with hearing loss in Europe. In addition to this mutation, mitochondrial genome has several targets for genetic defects associated with hearing loss in people with a long period aminoglycoside exposure during childhood. Eighty-eight probands and their kindred with hereditary and congenitally hearing loss diagnosed by audiological measurement were included in the study. The pedigrees of each kindred were prepared according to their family history. PCR amplifications followed by DNA sequence analyses of this gene were carried out in genomic DNA samples from each proband. The detected mutations were also searched in family members of probands similarly. 35delG change was confirmed by using BseLI restriction enzyme. The positions of 1555 and 7445 in mitochondrial DNA were tested by restriction enzyme analysis, using Alw26I and XbaI enzymes respectively. Furthermore, the control group consisted of 171 people without hearing loss was investigated by DNA sequence analyses on this gene for genetic variations and polymorphisms. Among the cases with hearing loss, 26.6% displayed mutations while 7.96% had polymorphisms. The detected mutations were as fallows: 35delG (%18.18), G380A (2.28%), A88G (1.14%), 247delTTC (1.14%), T269C (1.14%), 299delAT (1.14%), 358delGAG (1.14%). Besides, G79A (5.68%), G457A (1.14%), C570T (1.14%) polymorphisms have also been detected. No mutation has been found in mitochondrial genome for the corresponding positions. The frequency of 9 different SNPs was 15.78% in the control group. The most frequent SNPs were G79A (5.26%) and G457A (4.68%). In conclusion, this is the first study of this gene by DNA sequence analysis approach in cases with hearing loss in the Aegean region of Turkey. A novel mutation, 247delTTC in one proband and two novel SNPs (G647C, C292T) in the control group were detected.