| 摘要: | 自1996年聽障(Hearing loss)的基因陸續被發現，到目前為止已有五十九個基因涉及聽障。約有1/1000嬰兒再出生時或在小孩早期(即學習語言前Prelingual period)罹患重度(Severe or profound)聽障，其中約有60%個案是遺傳因素。目前已知許多基因的突變會導致聽障，各基因的致病機制不盡相同，非常複雜。本研究計畫將集中全力著重於CLDN14及TMPRSS3等基因的篩檢，以獲得CLDN14及TMPRSS3基因在台灣地區學習語言前非症候群感音神經聽障患者中所佔的比例和突變點之較完整的資料，並可作為遺傳諮詢之參考。同時將利用已完成之Cx基因族的資料庫進行全國性聽障基因篩檢服務。我們仍以學習語言前非症候群感音神經聽障患者為研究對象。樣本來自(1)聽力正常的人120位(2)台中啟聰學校聽障學童約有230名，先由耳鼻喉科醫師進行聽力鑑定及相關檢查排除環境及症候群因素。如有基因異常者，再進行家族追蹤研究。本計畫研究的方法主要利用PCR的方法將CLDN14及TMPRSS3擴增出來，並針對這些基因進行序列分析比對。本計畫的目的是希望能建立台灣地區CLDN14、TMPRSS3基因族在學習語言前聽障中所佔的比例，尋找一個快速的分子生物學診斷方法，建立一個全國性聽障基因篩檢模式，以降低台灣地區學習語言前聽障患者的發生。我們針對台中啟聰學校230位語言學習前非症候群聽障(Prelingual non- syndromic deafness)的學童作CLDN14、TMPRSS3基因分析發現有17位聽障學童有突變的發生，所佔的比例為7.39% (17/230)。在這17位病人中，有5位是CLDN14基因的突變所佔的比例為29.41% (5/17)、12位是TMPRSS3基因的突變所佔的比例為70.59% (12/17)。另外對於遺傳諮詢服務方面我們也完成了8個案例，在全國性聽障基因篩檢服務方面我們共收集了25個個案並完成了13個個案的分析，其中有5個個案在Cx基因族中有突變的發生，其餘的個案我們持續分析中。本研究的結論是我們已建立台灣地區語言學習前非症候群聽障孩童的CLDN14和TMPRSS3基因多型性和突變的資料庫，加上我們先前的對Cx基因族的分析結果，對於學習語言前費症候群聽障患者的研究有重大意義，綜合這些結果到目前為止合計發現有67位聽障患者在這些基因有突變的發生，所佔的比例為29.13% (67/230)。我們也開始利用所建立的資料庫進行Cx基因族的篩檢服務並完成遺傳諮詢手冊的建立，相信這些結果、技術和諮詢模式的建立將可提供學習語言前聽障患者的服務管道，以降低台灣地區學習語言前聽障患者的發生。
Approximately 1 in 1000 children at birth or before 2 years of age (the prelingual period) are affected by severe deafness, the prelingual non-syndromic deafness. In developed countries, 60% of children with such deafness has been determined to be of genetic origin. In order to evaluate the extent to which the CLDN14 and TMPRSS3 genes contributes to non-syndromic prelingual deafness in Taiwan, we have searched for mutations of these genes in 230 affected schoolchildren from National Taichung Deafness School. These children have also been referred to genetic counseling for deafness at Chung Shan Medical university Hospital. Of the 230 children with deafness, 17 patients carry mutated genes. We found that 5 patients possess mutations in the CLDN14 gene. These are 52A→G/WT(M18V), 167-168delGG 243C→T/WT (R81R), 424G→A/WT(D142N), and 687G→A/WT(T229T). In the case of TMPRSS3 gene, we found that 12 patients with different mutations. These are 406+38C→T/WT, 752T→C/WT (L184S), 822T→C/WT(C207C), 1395+15C→A/WT, 1454C→T/WT(A418V), 1470C→T/WT(A311A), 1134C→T/WT(14231), and 1548+11C→T/WT. In addition, we have also completed analysis of 8 deafness families carrying mutations in Cx gene family for genetic counseling and have collected 25 smaples of deafness patients from 3 hospitals for Cx gene family screening. Currently, we have already finished 13 deafness patients in Cx gene family screening. Of the 13 patients, 5 patients carry mutated genes. These are 370 C→T/WT in Cx30.3 gene, 396C→T/WT in Cx30 gene, 368C→A/WT in Cx26 gene, 807A→T/WT in Cx29 gene, and 976C→T/WT in Cx43 gene, respectively. We aim to continue screening for Cx gene family in deafness patients for the usein in genetic counseling. Our data are clearly informative for understanding the weight of genetic factors in prelingual non-syndromic sensorineural deafness in Taiwan and in genetic counseling of hearing loss. |
