Genetics of Presbyacus's and its clinical application

DFN3, and X-linked nonsyndromic mixed deafness is caused by mutations in BRN-4 gene，a POU transcription factor gene. By gene targeting technology Brn-4-deficient mice没有gross morphological changes observed in observed in created and found to exhibit profound deafnessthe conductive ossicles or cochlea虽然有一个drastic reduction in endocochlear potential (EP). Electron microscopy revealedsevere ultrastructural alterations in cochlear spiral ligament fibrocytes. Connexin 26 gene （GJB2）is known to be expressed in the cochlear fibrocytes and to play a important role in the auditory我们已经sequenced the GJB2 gene in 39 Japanese patients with prelingual sensorineuralhearing loss. Three novel mutations标识：单一核破坏（235delC）a 16 bp-deletion （176- 191del(16)）和a nonsense mutation (408c>a) in five unrelated patients.这些findings indicated that GJB2 mutations are also responsible for prelingual deafness in日本。These findings suggest These fibrocyteswhich are mesenchymal in origin and have been postulated to function in K - D1+ K - D1 homeostasis，may play a critical role in auditory function and show a major cause of the hereditary deafness。

DFN3, and X-linked nonsyndromic mixed deafness is caused by mutations in BRN-4 gene, which encodes a POU transcription factor gene. By gene targeting technology Brn-4-deficient mice were created and found to exhibit profound deafness. No gross morphological changes were observed in the conductive ossicles or cochlea, although there was a drastic reduction in endocochlear potential (EP). Electron microscopy revealed severe ultrastructural alterations in cochlear spiral ligament fibrocytes. Connexin 26 gene (GJB2) is known to be expressed in the cochlear fibrocytes and to play a important role in the auditory function. We have sequenced the GJB2 gene in 39 Japanese patients with prelingual sensorineural hearing loss. Three novel mutations were identified : a single nucleotide deletion (235delC), a 16 bp-deletion (176-191 del (16)) and a nonsense mutation (408c>a) in five unrelated patients. These findings indicated that GJB2 mutations are also responsible for prelingual deafness in Japan. These findings suggest that these fibrocytes, which are mesenchymal in origin and have been postulated to function in KィイD1+ィエD1 homeostasis, may play a critical role in auditory function and show a major cause of the hereditary deafness.