[Clinical and molecular genetic analysis of monozygotic twins displaying stapes gusher syndrome (DFN3)].

BACKGROUND: DFN3 ( "stapes gusher") is the most frequent form of X-linked hearing impairment. It accounts for up to 0.5% of all cases of severe childhood hearing disorders. PATIENTS AND METHODS: Monozygotic twins with suspected stapes gusher syndrome, their mother, and control individuals were analyzed clinically and genetically.
RESULTS: The clinical investigations confirmed a DFN3 phenotype in both brothers who displayed all typical symptoms. A molecular genetic investigation of the POU3F4 gene, which plays an essential role in the development of DFN3, was also performed. No chromosomal aberrations within the coding region of POU3F4were detected. Since several authors have described mutations in the 5' untranslated region of the gene also resulting in a DFN3 phenotype, we screened this area by microsatellite analysis and detected a double deletion localized in the critical interval. This is the first description of a double deletion in the non-coding region of POU3F4 leading to DFN3 phenotype.
CONCLUSION: Interestingly, in spite of having an identical genotype, the twins displayed significant phenotypic differences. This underlines the importance of exogenous factors in the development of inherited pathological processes.