一个常染色体显性遗传低频感音神经性聋家系听力学及遗传学特征分析

Genetic and Audiological Characteristics of a Chinese Family with Autosamal Dominant Hereditary Non-syndromic Low-frequency Sensorineural Hearing Loss

孙艺;卢宇;朱玉华;程静;李建忠;冀飞;王荣光;袁慧军;

1:中国人民解放军总医院耳鼻咽喉科研究所

摘要
目的分析一个常染色体显性遗传性聋家系的临床听力学特征及遗传规律。方法对一个常染色体显性遗传低频感音神经性聋家系28名成员进行病史采集、体检及纯音测听、声导抗检查并绘制系谱图。其中,5名患者进行耳声发射、听性脑干反应检查,2名患者进行前庭功能及颞骨CT扫描检查以排除听神经病及听觉系统的其他病变。全部成员均应用微卫星标记对DFNA21个位点23个基因进行初步筛查,数据分析采用连锁分析方法。结果该耳聋家系(命名为BJ-L046)遗传方式为常染色体显性遗传,耳聋患者表现为迟发型的、渐进性的、以低频下降为主的听力损失,发病年龄528岁,早期以低频损失为主,听力曲线呈上升型,随着年龄增长逐渐累及全频听力,听力曲线由上升型变为平坦型。全部家系成员FNA21个位点23个基因筛查均为阴性。结论该耳聋家系为常染色体显性遗传方式,表现为低频感音神经性聋,数据连锁分析无阳性发现,初步排除了21个DFNA位点23个已知基因。
关键词
常染色体显性遗传;遗传性聋;低频;表型;家系;微卫星标记;连锁分析
基金项目(Foundation):
国家高技术研究发展计划(“863”高科技项目)资助(2007AA02Z466)
作者
孙艺;卢宇;朱玉华;程静;李建忠;冀飞;王荣光;袁慧军;
参考文献

1 Van Camp G,Smith RJH.2008.Hereditary Hearing Loss Homep-age.Http://webho1.ua.ac.be/hhh/.

2 Van Camp G,Smith RJH.Recommendations for the descrip-tion of genetic and audiological data for families with nonsyn-dromic hereditary hearing impairment.Hereditary HearingLoss Homepage.http://webho1.ua.ac.be/hhh/.

3 Dawn Teare M,Barrett JH.Genetic linkage studies[J].Lan-cet,2005,366:1 036.

4 Leon PE,Ronilla JA,Sanchez JR,et al.Low frequency he-reditary deafness in man with childhood onset[J].AM J HumGenet,1981,33:209.

5 Leon PE,Raventos H,Lynch E,et al.The gene for an inheri-ted form of deafness maps to chromosome 5q31[J].Proc NatlAcad Sci USA,1992,89:5 181.

6 Lynch ED,Lee MK,Morrow JE,et al.Nonsyndromic deaf-ness DFNA1 associated with mutation of a human homolog ofthe Drosophila gene diaphanous[J].Science,1997,278:1 315.

7 Lesperance MM,Hall JW,Bess FH,et al.A gene for autoso-mal dominant nonsyndromic hereditary hearing impairmentmaps to 4p16.3[J].Hum Mol Genet,1995;4:1967.

8 Van Camp G,Kunst H,Flothmann K,et al.A gene for auto-somal dominant hearing impairment(DFNA14)maps,to a re-gion on chromosome 4p16.6 that does not overlap the DFNA6locus[J].J Med Genet,1999,36:532.

9 Bespaloca IN,Van Camp G,Bom SJ,et al.Mutations in theWolfram syndrome 1 gene(WFS1)are a common cause of lowfrequency sensorineural hearing loss[J].Hum Mol Genet,2001,10:2 501.

10 Young TL,Ices E,Lynch E,et al.Non-syndromic pro-gressive hearing loss DFNA38 is caused by heterozygous mis-sense mutation in the Wolfram syndrome gene WFS1[J].Hum Mol Genet,2001,10:2 509.

11 Cryna K,Pfister M,Pennings RJ,et al.Mutations in theWFS1 gene that cause low-frequency sensorineural hearingloss are small non-inactivating mutations[J].Hum Genet,2002,110:389.

12 Liu XZ,Walsh J,Mburu P,et al.Mutations in the myosinVIIA gene cause non-syndromic recessive deafness[J].NatGenet,1997,16:188.

13 Luijendijk MWJ,VanWijk E,Bischoff AMLC,et al.Identi-fication and molecular modelling of a mutation in the motorhead domain of myosin VIIA in a family with autosomal domi-nant hearing impairment(DFNA11)[J].Hum Genet,2004,115:149.

14 Street VA,Kallman JC,Kiemele KL.Modifier controls se-verity of a novel dominant low-frequency myosin VIIA(MYO7A)auditory mutation[J].J Med Genet,2004,41:e62.

15 Gurtler N,Kim Y,Mhatre A,et al.DFNA54,a third lo-cus for low-frequency hearing loss[J].J Mol Med,2004,82:775.