[Hereditary hearing impairment. Mutation analysis of connexin 26 and POU3F4 genes in Icelanders with nonsyndromic hearing impairment.].
AIMS: Mutations in the connexin 26 (Cx26) gene have recently been shown to be a major cause of hereditary nonsyndromic sensorineural hearing impairment in Caucasians. Studies indicate that approximately 10-30% of all childhood deafness are due to Cx26 mutations and the most frequently observed mutation is Cx26 35delG. Mutations in the POU3F4 are the most common cause of X-linked nonsyndromic hereditary hearing impairment. The aim of our study was to determine presence and type of Cx26 and POU3F4 mutations in an Icelandic cohort with nonsyndromic hearing impairment. MATERIAL AND METHODS: All 15 individuals participating in the study, fulfilled the criteria of severe congenital nonsyndromic hearing impairment of unknown cause and the hearing loss was documented by audiologic testing in a clinical facility. Eleven had a family history and four were sporadic cases. All exons of the Cx26 and POU3F4 genes were amplified using PCR and six pairs of primers. The amplified DNA fragments were screened for sequence variations using enzymatic mutation detection and the nucleotide sequence of fragments showing signs of variation was determined. RESULTS AND CONCLUSIONS: Using the methods described above four distinct sequence variations were detected in the Cx26 gene. The 35delG allele causing hereditary recessive hearing impairment was identified in one homozygous and one heterozygous individual. The heterozygous 35delG individual was also shown to carry the recessive allele 358-360delGAG (E). A missense mutation, 101Teth C (M34T), supposed to cause autosomal dominant form of hearing impairment with variable penetrance, was detected in one heterozygous individual. A novel sequence variation without known clinical significance, -63Teth G, was found in the 5'-noncoding sequence in one control sample. No mutations were detected in the POU3F4 gene.