Genetics of Presbyacus's and its clinical application

DFN 3，和X-连接的非综合性混合缺陷导致了BRN-4基因中的突变，其中编码了POU转录因子基因。通过基因靶向技术Brn-4-可靠的老鼠已经被创造并找到了以展示的潜在缺陷。在Conductive ossicles或Cochlea中没有明显的形态变化，在内科氏潜力中可能有一个粗略的减少（EP）。Electron microscopy揭示了Cochlear spiral ligament fibrocytes中的多个超结构替代品。Connexin 26 gene （GJB2） is known to be expressed in the cochlear fibrocytes and to play a important role in the auditory function。我们在39名日本患者中对GJB 2基因进行了测序，导致听力损失。三部小说已被确认：一个单一的核苷酸变异（235 delC），一个16 bp变异（176-191 del （16））和一个无意义变异（408 c>a）在五个不相关的患者中。这些发现表明，GJB 2突变对日本的语言前死亡率也是负责任的。这些发现提出了这些纤维细胞的原因，因为它们起源于中间，并且已经被推迟到KIE D1+ IE D1 homeostasis中的功能，可以在auditory函数中扮演一个关键角色，并显示一个主要原因的遗传缺陷。

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.