西北地区非综合征型耳聋患者GJB2、SLC26A4基因突变的分子流行病学研究

An Investigation of GJB2,SLC26A4 Gene Mutations in Nonsyndromic Hearing Loss in the Northwest of China

郭玉芬;刘晓雯;关静;徐百成;韩明鲲;赵翠;赵亚丽;王大勇;兰兰;鲍晓林;王秋菊;

1:兰州大学第二医院耳鼻咽喉-头颈外科

2:解放军总医院耳鼻咽喉-头颈外科、解放军总医院耳鼻咽喉科研究所

3:解放军总医院耳鼻咽喉-头颈外科、解放军总医院耳鼻咽喉科研究所

摘要
目的探讨GJB2、SLC26A4基因突变在中国西北地区非综合征型耳聋(nonsydromic hearing impair-ment,NSHI)患者中的突变频率及主要的突变方式。方法采集中国西北地区801例非综合征型耳聋患者血样,应用PCR技术扩增GJB2基因的编码区和SLC26A4基因第7、19外显子,PCR产物进行直接测序,运用DNAS-tar5.0或BioEdit软件进行测序结果分析。结果801例NSHI患者中共检测到125例发生GJB2基因突变,突变率为15.61%(125/801),其中双等位基因(纯合或复合杂合)突变率为8.99%(72/801),235delC约占所有突变的78.79%(156/198)。101人发生SLC26A4基因(P7、P19)IVS7-2A>G、H723R和T721M突变,突变率为12.61%(101/801),其中双等位基因突变率为5.12%(41/801)。结论在中国西北地区NSHI患者中,235delC是GJB2基因最常见的突变方式,IVS7-2A>G和H723R是SLC26A4基因主要的突变方式。
关键词
聋;突变;GJB2基因;SLC26A4基因;等位基因
基金项目(Foundation):
国家863项目(2006AA02Z181);; 国家自然基金面上项目(30672310,30771203 & 30771857);; 高等学校全国优秀博士学位论文作者专项资金资助项目(200463);; 军队“十一五”杰出人才项目(06J018);; 北京市科技计划重大项目(D0906005040291);; 国家973项目(2007CB507400);; 北京市重大专项课题项目(7070002);; 国家“十一五”科技支撑计划(2006BAI02B06 & 2007BAI18B12);; 甘肃省中青年基金课题(3YS061-A25-012)联合资助
作者
郭玉芬;刘晓雯;关静;徐百成;韩明鲲;赵翠;赵亚丽;王大勇;兰兰;鲍晓林;王秋菊;
参考文献

1 Mazzoli M,Van Camp G,Newton V,et al.Recommendationsfor the description of genetic and audiological data for familieswith nonsyndromic hereditary hearing impairment[J].Audio-logical Medicine,2003,1:148.

2 Wang QJ,Zhao YL,Rao SQ,et al.A distinct spectrum ofSLC26A4 mutations in patients with enlarged vestibular aque-duct in China[J].Clinical Genetics,2007,72:245.

3 Wu CC,Yeh TH,Chen PJ,et al.Prevalent SLC26A4 muta-tions in patients with enlarged vestibular aqueduct and/orMondini dysplasia:a unique spectrum of mutations in Taiwan,including a frequent founder mutation[J].Laryngoscope,2005,115:1 060.

4 Coyle B,Reardon W,Herbrick JA,et al.Molecular analysisof the PDS gene in pendred syndrome[J].Hum Mol Genet,1998,7:1 105.

5 Kenneson AK,Van Naarden B,Boyle C.GJB2(connexin 26)variants and nonsyndromic sensorineural hearing loss:a hugereview[J].Genet Med,2002,4:258.

6 Liu XZ,Xia XJ,Ke XM,et al.The prevalence of connexin 26(GJB2)mutations in the Chinese population[J].Hum Genet,2002,111:394.

7 Hwa HL,Ko TM,Hsu CJ,et al.Mutation spectrum of theconnexin 26(GJB2)gene in Taiwanese patients with prelin-gual deafness[J].Genet Med,2003,5:161.

8李庆忠,王秋菊,迟放鲁,等.中国散发听力损失患者中GJB2基因突变分子流行病学研究[J].中国眼耳鼻喉科杂志,2006,6:310.

9 Taylor JP,Metcalfe RA,Watson PF,et al.Mutations of thePDS gene,encoding pendrin,are associated with protein mis-localization and loss of iodide efflux:implications for thyroiddysfunction in Pendred syndrome[J].J Clin EndocrinolMetab,2002,87:1 778.

10 Campbell C,Cucci RA,Prasad S,et al.Pendred syndrome,DFNB4,and PDS/SLC26A4 identification of eight novel mu-tations and possible genotype-phenotype correlations[J].Hum Mutat,2001,17:403.

11 Tsukamoto K,Suzuki H,Harada D,et al.Distribution andfrequencies of PDS(SLC26A4)mutations in Pendred syn-drome and nonsyndromic hearing loss associated with en-larged vestibular aqueduct:a unique spectrum of mutations inJapanese[J].Eur J Hum Genet,2003,11:916.

12 Park HJ,Lee SJ,Jin HS,et al.Genetic basis of hearing lossassociated with enlarged vestibular aqueducts in Koreans[J].Clin Genet,2005,67:160.