常染色体显性遗传性聋家系遗传学特征及外显子组测序分析

发布时间：2018-02-01 14:05

  本文关键词： 常染色体显性遗传 感音神经性聋 全外显子组测序 基因　出处：《听力学及言语疾病杂志》2014年04期 　论文类型：期刊论文

【摘要】：目的分析常染色体显性遗传性聋家系的听力学及遗传学表型特征,并鉴定其致聋基因。方法对一个常染色体显性遗传非综合征型感音神经性聋家系进行病史采集和听力学检测,绘制耳聋家系系谱图,提取受检者的基因组DNA;对先证者进行外显子组测序,并结合家系的遗传学特征及患病者的听力学特征等进行分析,应用Sanger测序对筛选出的候选变异位点进行验证。结果该家系共五代27人(男13人,女14人),现存19人;患感音神经性聋者10人,表型不确定者1人,现存明确感音神经性聋者7人,发病年龄10~30岁,均表现为双耳对称性进行性中度至重度感音神经性聋,听阈曲线为下降型或平坦型;共检测到6个已知耳聋基因的突变位点及900多个未知基因的变异位点,应用Sanger测序对检测到的EYA4(c.1486AT)、MYO7A(c.3602GC)和ESPN(c.2225CT)已知耳聋基因的突变位点及DNMT1(c.4381CT)、BMP2(c.393AT)、TP63(c.854GA)和RAI1(c.4162GA)4个可疑的变异予以验证并排除了其致病的可能性。结论该家系符合常染色体显性遗传非综合征型聋遗传学特征,表现为中度至重度感音神经性聋;对已发现的3个已知耳聋基因突变位点及4个可疑的变异位点进行筛查,未发现明确的致病位点,提示其致聋基因可能为新的致聋基因;对于未知基因的鉴定,最好选取2个以上样本进行外显子组测序。
[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.
【作者单位】： 中国人民解放军总医院耳鼻咽喉头颈外科耳鼻咽喉研究所;
【基金】：国家自然科学基金重点项目(No.81030017)资助
【分类号】：R764
【正文快照】： 导致耳聋的常见病因中,环境因素约占40%,遗传因素约占60%。绝大多数的遗传性聋为单基因致病,只有少数耳聋由多基因联合致病。耳聋具有明显的遗传异质性,即同一表型的耳聋可由不同的基因或突变引起,而不同表型又可由同一致病基因所引起。遗传性聋分为综合征型(30%)及非综合征型，

本文编号：1482036