本文選題：耳聾 + 前庭　； 參考：《南京醫(yī)科大學(xué)學(xué)報(自然科學(xué)版)》2016年03期

【摘要】：目的:對1個遺傳性耳聾伴前庭功能障礙家系進(jìn)行遺傳方式、表型特征及致病基因的分析,以研究其分子病因。方法 :對門診1例遺傳性聾伴眩暈患者進(jìn)行家系調(diào)查、病史收集及相應(yīng)的聽力學(xué)和前庭功能檢查。利用目標(biāo)基因捕獲和大規(guī)模平行測序技術(shù),對家系先證者進(jìn)行可能致病突變篩查,包括靶向104種與遺傳性聽力損失相關(guān)的基因和3個micro RNA分子。進(jìn)一步對獲得的候選突變基因進(jìn)行編碼區(qū)序列驗證分析。結(jié)果:目標(biāo)基因捕獲測序結(jié)果發(fā)現(xiàn)先證者COCH基因第11外顯子上存在c.1458CG(p.T352S)的雜合突變。進(jìn)一步對家系中所有患者和有血緣關(guān)系的正常個體進(jìn)行了遺傳共分離分析,發(fā)現(xiàn)該雜合突變在該家系中僅有Ⅰ2、Ⅱ1、Ⅱ5、Ⅱ9、Ⅱ13和Ⅳ1存在相同的雜合突變,而Ⅱ11和Ⅲ1表現(xiàn)為該突變的純合子,表明該雜合突變不存在共分離現(xiàn)象,因此可以排除其為該家系致病突變的可能性。對先證者Ⅲ14COCH基因全部12個外顯子的序列測定結(jié)果未發(fā)現(xiàn)其他突變。結(jié)論:此家系為常染色體顯性遺傳性非綜合征型耳聾伴前庭功能障礙,但初步篩查結(jié)果未發(fā)現(xiàn)已知耳聾相關(guān)基因,包括COCH基因的可疑致病突變。因此,該家系的分子病因可能存在一新基因的突變。
[Abstract]:Objective: to study the molecular etiology of hereditary deafness with vestibular dysfunction (vestibular dysfunction) by analyzing its genetic pattern phenotypic characteristics and pathogenetic genes. Methods: a case of hereditary deafness with vertigo in outpatient department was investigated in family history and audiology and vestibular function were examined. Objective gene capture and large-scale parallel sequencing were used to screen possible pathogenicity mutations in probands including 104 genes and 3 micro RNA molecules related to hereditary hearing loss. Further, the candidate mutation gene was analyzed by coding sequence verification. Results: the results of target gene capture and sequencing showed that there was a heterozygous mutation in exon 11 of the proband COCH gene. Furthermore, the genetic cosegregation analysis of all the patients in the family and the normal individuals with blood relationship showed that only 鈪，

本文編號：1909290