Hearing impairment is the most common sen-sori-neural disorder in humans, about 1 in 1000 newborns being affected by severe to profound deaf­ness at birth or during early childhood. In infants, it may have dramatic effects on language acquisition and on social and working lives. Genetic causes ac­count for about half of these cases, the remainder being due to environmental factors [1]. Non syn-dromic hereditary hearing impairment is extremely heterogeneous genetically. More than 130 different gene loci have been identified [2,3]. These include 54 loci associated with autosomal dominant inheri­tance (DFNA), 67 loci with autosomal recessive in­heritance (DFNB), five loci that are X-chromosome linked and four that occur in mitochondrial DNA. Within these loci, approximately 46 genes have been found to be responsible for hearing loss. They encode a wide variety of protein classes including transcription factors, cytoskeletal and extracellular matrix components, and ion channels.

 

The gene with most significant impact on the population genetics and genetic counseling is the GJB2 gene located on chromosome 13q12, muta­tions in which account for about 50% of all congen­ital cases of hearing impairment. This gene encodes gap junction protein connexin 26 which is implicat­ed in intracellular communication. A frequent point mutation is 35delG, deletion of the sixth G within a stretch of Gs at position 30-35 [4]. This mutation is frequent in Mediterranean countries, with a car­rier frequency of 2.3-4.0%. Over 100 other muta­tions have been found in the GJB2 gene, of which 167delT, 235delC and R143W are most common in Ashkenazi Jews, and Japanese and Ghanaian popu­lations [5].

Many patients with autosomal recessive hear­ing impairment carry only one mutant GJB2 allele. Some families have clear evidence of linkage to the DFNB1 locus, which contains the GJB2 and GJB6 genes, which encode connexin 30 [6]. A 342 kb deletion involving the GJB6 gene, delD 13S1830, has been found to be very common in non syndro-mic hearing-impaired patients from Spain, France, Israel, the United Kingdom and Brazil, which also suggests a possible GJB2/GJB6 digenic pattern of inheritance of deafness [7].