本文關鍵詞： 常染色體顯性遺傳 感音神經(jīng)性聾 全外顯子組測序 基因　出處：《聽力學及言語疾病雜志》2014年04期 　論文類型：期刊論文

【摘要】：目的分析常染色體顯性遺傳性聾家系的聽力學及遺傳學表型特征,并鑒定其致聾基因。方法對一個常染色體顯性遺傳非綜合征型感音神經(jīng)性聾家系進行病史采集和聽力學檢測,繪制耳聾家系系譜圖,提取受檢者的基因組DNA;對先證者進行外顯子組測序,并結合家系的遺傳學特征及患病者的聽力學特征等進行分析,應用Sanger測序對篩選出的候選變異位點進行驗證。結果該家系共五代27人(男13人,女14人),現(xiàn)存19人;患感音神經(jīng)性聾者10人,表型不確定者1人,現(xiàn)存明確感音神經(jīng)性聾者7人,發(fā)病年齡10~30歲,均表現(xiàn)為雙耳對稱性進行性中度至重度感音神經(jīng)性聾,聽閾曲線為下降型或平坦型;共檢測到6個已知耳聾基因的突變位點及900多個未知基因的變異位點,應用Sanger測序對檢測到的EYA4(c.1486AT)、MYO7A(c.3602GC)和ESPN(c.2225CT)已知耳聾基因的突變位點及DNMT1(c.4381CT)、BMP2(c.393AT)、TP63(c.854GA)和RAI1(c.4162GA)4個可疑的變異予以驗證并排除了其致病的可能性。結論該家系符合常染色體顯性遺傳非綜合征型聾遺傳學特征,表現(xiàn)為中度至重度感音神經(jīng)性聾;對已發(fā)現(xiàn)的3個已知耳聾基因突變位點及4個可疑的變異位點進行篩查,未發(fā)現(xiàn)明確的致病位點,提示其致聾基因可能為新的致聾基因;對于未知基因的鑒定,最好選取2個以上樣本進行外顯子組測序。
[Abstract]:Objective to analyze the audiological and genetic phenotypic characteristics of autosomal dominant hereditary deafness. Methods A family of autosomal dominant non-syndromic sensorineural hearing loss was collected and examined by audiology, and the pedigree of deafness pedigree was drawn. The genomic DNA of the subject was extracted. The exon sequence of the proband was sequenced, and the genetic characteristics of the families and the audiological characteristics of the patients were analyzed. The candidate mutation sites were confirmed by Sanger sequencing. Results 27 individuals (13 males, 14 females, 19 extant) from this family were selected. There were 10 cases of sensorineural deafness, 1 case of phenotypic uncertainty and 7 cases of existing definite sensorineural deafness. The onset age was 10 ~ 30 years old. All of them showed progressive moderate to severe sensorineural hearing loss with bilateral symmetry. The hearing threshold curve is descending or flat. Six mutation sites of known deafness gene and more than 900 unknown gene mutation sites were detected. EYA4C1486ATdetected by Sanger sequencing. The mutation site of the deafness gene and the DNMT1 / c. 4381CTare known to be MYO7AN c. 3602GC) and ESPNs c. 2225CT. BMP2 / c. 393AT. TP63 (c. 854GA) and RAI1 (c. 4162GA). Four suspicious mutations were verified and the possibility of pathogenicity was excluded. Conclusion the genetic characteristics of autosomal dominant non-syndromic deafness are conformed to this pedigree. The symptoms were moderate to severe sensorineural deafness. Three known mutation sites of deafness gene and four suspicious mutation sites were screened, and no definite pathogenicity loci were found, suggesting that the deafness gene may be a new deafening gene. For the identification of unknown genes, it is better to select more than 2 samples for exon sequencing.
【作者單位】： 中國人民解放軍總醫(yī)院耳鼻咽喉頭頸外科耳鼻咽喉研究所;
【基金】：國家自然科學基金重點項目(No.81030017)資助
【分類號】：R764
【正文快照】： 導致耳聾的常見病因中,環(huán)境因素約占40%,遺傳因素約占60%。絕大多數(shù)的遺傳性聾為單基因致病,只有少數(shù)耳聾由多基因聯(lián)合致病。耳聾具有明顯的遺傳異質性,即同一表型的耳聾可由不同的基因或突變引起,而不同表型又可由同一致病基因所引起。遺傳性聾分為綜合征型(30%)及非綜合征型，

本文編號：1482036