| Research Abstract |
The recent identification of various genes responsible for hearing loss has shed light on the mechanisms of hearing and enables the ENT clinician to apply molecular diagnosis by genetic testing. The present study was conducted to clarify the genetic background of deafness and to apply the basic science to the clinic. We focused on 1) new genes responsible for deafness, 2) the genetic epidemiology of deafness genes, 3) genotype/phenotype correlations, 4) genetic testing suitable for the clinical situation, 5) genetic counseling. In this study, among the genes highly expressed in the inner ear, we found new genes responsible for deafness, including mu-crystallin, KIAA-1199, COL9A3, and ATP1A2. By screening 2000 deafness patients, GJB2, PDS (SLC26A4), and the 1555A>G mitochondrial mutation were found to be the major causes of hearing loss in Japanese patients. Spectrums of GJB2 and PDS (SLC26A4) mutations found in the Japanese population, which is probably representative of other Asian populations, were quite different from those reported in the populations with European ancestry. This suggests that each racial population may have a unique epidemiology of deafness genes and the ethnic background of and individual should be borne in mind when genetic testing is performed.
Genotype/phenotype correlation found in the patients with GJB2 mutations was evaluated. In our series, the patients with the V37I mutation had a milder phenotype than those with 235delC mutation.
Therefore, evaluation of genotype of the patients could predict their hearing prognosis by genetic testing. We also established a screening system based on the invader assay and a genetic counseling section in Shinshu Univ. Hospital.
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