一个常染色体显性遗传非综合征型聋家系的听力学及遗传学特征分析

Genetic and Audiological Characteristics of An Autosomal Dominant Nonsyndromic Deafness Kindred

牛志杰;蒋璐;梅凌云;冯永;陈红胜;贺楚峰;刘亚兰;王雪萍;刘畅;熊俊;

1:中南大学湘雅医院耳鼻咽喉头颈外科

2:中南大学湘雅医院耳鼻咽喉重大疾病研究湖南省重点实验室

3:中南大学医学遗传学国家重点实验室

摘要
目的分析一个常染色体显性遗传非综合征型聋家系的听力学和遗传学特征。方法对收集到的一个常染色体显性遗传非综合征型聋家系成员进行家系调查、听力学检测和全身体格检查,绘制家系图谱,整理、分析家系成员的听力学和遗传学特征;提取外周血DNA,对已知常见耳聋基因GJB2、GJB3、COCH、EYA4以及线粒体DNA全序列进行筛查。结果该家系由5代53名成员组成,现存4代42人,耳聋患者11人;耳聋表型连续遗传,男女均可患病,符合常染色体显性遗传规律,均表现为对称性语后感音神经性聋(1236岁之间发病),起初为高频听力下降,随着年龄的增长,逐渐累及中低频听力。已知常见致聋基因全编码序列突变检测分析无阳性发现。结论该常染色体显性遗传非综合征型聋家系中耳聋者表现为对称性、迟发性、进行性、高频下降为主的语后感音神经性聋。
关键词
常染色体显性遗传;遗传性聋;基因突变;家系
基金项目(Foundation):
国家重大科学研究计划项目(Grant No.2014CB943003);; 国家自然科学基金(Grant No.81300833);; 湖南省自然科学基金青年基金(Grant No.13JJ4023)资助资助
作者
牛志杰;蒋璐;梅凌云;冯永;陈红胜;贺楚峰;刘亚兰;王雪萍;刘畅;熊俊;
参考文献

1 Morton CC,Nance WE.Newborn hearing screening--a silent revolution[J].N Engl J Med,2006,354:2151.

2 Kenneson A,Cannon MJ.Review and meta-analysis of the epidemiology of congenital cytomegalovirus(CMV)infection[J].Rev Med Virol,2007,17:253.

3 Van Camp G,Willems PJ,Smith RJ.Nonsyndromic hearing impairment:unparalleled heterogeneity[J].Am J Hum Genet,1997,60:758.

4 王鸿涵,冯永,王行炜,等.一个迟发性非综合征型常染色体显性遗传性聋家系表型特征及致病基因初步探讨[J].听力学及言语疾病杂志,2012,20:309.

5 Hilgert N,Smith RJ,Van Camp G.Forty-six genes causing nonsyndromic hearing impairment:which ones should be analyzed in DNA diagnostics[J]?Mutat Res,2009,681:189.

6 李丽娜,李庆忠,武文明,等.散发高频听力下降人群中KCNQ4基因的突变筛查[J].听力学及言语疾病杂志,2007,15:25.

7 顾瑞.纯音测听[M].见:姜泗长,闫承先,主编.现代耳鼻咽喉科学.天津:天津科学技术出版社,1994.11~12.

8 王秋菊,译.关于非综合征型遗传性听损伤家系遗传学及听力学描述术语建议案[J].中华耳科学杂志,2003,1:46.

9 Petersen MB,Willems PJ.Non-syndromic,autosomal-recessive deafness[J].Clinical Genetics,2006,69:371.

10 孙开来,赵彦艳,熊第志,译.医学遗传学原理[M].北京:科学出版社,2001.190~197.

11 Estivill X,Fortina P,Surrey S,et al.Connexin-26mutations in sporadic and inherited sensorineural deafness[J].Lancet,1998,351:394.

12 Angeli S,Lin X,Liu XZ.Genetics of Hearing and Deafness[J].The Anatomical Record:Advances in Integrative Anatomy and Evolutionary Biology,2012,295:1812.

13 Yan D,Park HJ,Ouyang XM,et al.Evidence of a founder effect for the 235delC mutation of GJB2(connexin 26)in east Asians[J].Hum Genet,2003,114:44.

14 Liu XZ,Pandya A,Angeli S,et al.Audiological features of GJB2(connexin 26)deafness[J].Ear Hear,2005,26:361.

15 Green GE,Mueller RF,Cohn ES,et al.Audiological manifestations and features of connexin 26deafness[J].Audiological Medicine,2003,1:5.

16 Xia JH,Liu CY,Tang BS,et al.Mutations in the gene encoding gap junction protein beta-3associated with autosomal dominant hearing impairment[J].Nat Genet,1998,20:370.

17 Lopez-Bigas N,Olive M,Rabionet R,et al.Connexin 31(GJB3)is expressed in the peripheral and auditory nerves and causes neuropathy and hearing impairment[J].Hum Mol Genet,2001,10:947.

18 Richard G,Smith LE,Bailey RA,et al.Mutations in the human connexin gene GJB3cause erythrokeratodermia variabilis[J].Nat Genet,1998,20:366.

19 Robertson NG,Lu L,Heller S,et al.Mutations in a novel cochlear gene cause DFNA9,a human nonsyndromic deafness with vestibular dysfunction[J].Nat Genet,1998,20:299.

20 Wayne S,Robertson NG,DeClau F,et al.Mutations in the transcriptional activator EYA4cause late-onset deafness at the DFNA10locus[J].Hum Mol Genet,2001,10:195.

21 Fischel-Ghodsian N,Prezant TR,Chaltraw WE,et al.Mitochondrial gene mutation is a significant predisposing factor in aminoglycoside ototoxicity[J].Am J Otolaryngol,1997,18:173.

22 Shearer AE,DeLuca AP,Hildebrand MS,et al.Comprehensive genetic testing for hereditary hearing loss using massively parallel sequencing[J].Proc Natl Acad Sci USA,2010,107:21104.

23 王洪阳,王秋菊.目标区域捕获联合新一代测序技术在遗传性聋研究中的应用及发展前景[J].听力学及言语疾病杂志,2014,22:531.