200例非综合征型聋患者GJB3和GJB6基因突变分析

GJB3 and GJB6 Genes Screening in 200 Non-Syndromic Hearing Impairment Patients

陈垲钿;宗凌;周蔚;刘敏;姜鸿彦;

1:中山大学附属第一医院耳鼻咽喉科医院

2:中山大学耳鼻咽喉科学研究所

摘要
目的研究广东、湖南和广西三省非综合征型聋患者GJB3和GJB6基因突变的特征。方法选择200例来自广东、湖南和广西三省的非综合征型聋患者,提取外周血DNA,PCR扩增后,进行GJB3、GJB6基因编码区测序和GJB6大片段缺失del(GJB6-D13S1830)及del(GJB6-D13S1854)突变检测。结果 200例患者中发现GJB3 580G>A杂合突变2例,其中1例为GJB2 109G>A和GJB3 580G>A复合杂合突变,250G>A杂合突变1例,474G>A杂合突变1例,357C>T杂合突变35例,纯合突变1例,474G>A为首次发现。GJB3等位基因突变频率为1%(4/400)。未发现GJB6基因突变。结论本组广东、湖南和广西三省非综合征型聋患者GJB3基因等位基因突变率为1%;GJB6基因突变致聋罕见。
关键词
非综合征型聋;GJB3;GJB6
基金项目(Foundation):
国家基础科学研究973项目(2011CB504502);; 国家自然基金项目(30973306);; 广东省重点自然基金项目(8251008901000016)联合资助
作者
陈垲钿;宗凌;周蔚;刘敏;姜鸿彦;
参考文献

1 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.

2 Guo YF,Liu XW,Guan J,et al.GJB2,SLC26A4and mitochon-drial DNA A1555G mutations in prelingual deafness in Northern Chinese subjects[J].Acta Otolaryngol,2008,128:297.

3戴朴,于飞,韩冰,等.中国不同地区和种族重度感音神经性聋群体热点突变的分布和频率研究[J].中华耳鼻咽喉头颈外科杂志,2007,42:804.

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

5 Marlin S,Feldmann D,Blons H,et al.GJB2and GJB6muta-tions genotypic and phenotypic correlations in a large cohort of hearing-impaired patients[J].Arch Otolaryngol Head Neck Surg,2005,131:481.

6 Liu XZ,Yuan Y,Yan D,et al.Digenic inheritance of non-syndromic deafness caused by mutations at the gap junction proteins Cx26and Cx31[J].Hum Genet,2009,125:53.

7李庆忠,王秋菊,赵立东,等.国人非综合征型遗传性聋患者GJB3基因突变分析[J].听力学及言语疾病杂志,2005,13:145.

8韩东一,李庆忠,兰兰,等.中国散发耳聋患者GJB6基因的突变筛查[J].中国耳鼻咽喉头颈外科,2006,13:670.

9袁永一,黄德亮,戴朴,等.中国非综合征遗传性聋人群GJB6基因突变分析[J].临床耳鼻咽喉头颈外科杂志,2007,21:3.

10黄选兆,汪吉宝,孔维佳,主编.实用耳鼻咽喉头颈外科学(第2版)[M].北京:人民卫生出版社,2008.1 005~1 006.

11 Del Castillo FJ,Rodríguez-Ballesteros M,Alvarez A,et al.A novel deletion involving the connexin-30gene,del(GJB6-d13s1854),found in trans with mutations in the GJB2gene(connexin-26)in subjects with DFNB1non-syndromic hearing impairment[J].J Med Genet,2005,42:588.

12 Pollak A,Skórka A,Mueller-Malesińska M,et al.M34T and V37Imutations in GJB2associated hearing impairment:evidence for pathogenicity and reduced penetrance[J].Amer-ican Journal of Medical Genetics Part A,2007,143A:2 534.

13 Huculak C,Bruyere H,Nelson TN,et al.V37Iconnexin 26 allele in patients with sensorineural hearing loss:evidence of its pathogenicity[J].Am J Med Genet A,2006,140:2 394.

14 Del Castillo I,Moreno-Pelayo MA,Del Castillo FJ,et al.Prevalence and evolutionary origins of the del(GJB6-D13S1830)mutation in the DFNB1locus in hearing-im-paired subjects:a multicenter study[J].Am J Hum Genet,2003,73:1 452.

15 Rodriguez-Paris J,Schrijver I.The digenic hypothesis un-raveled:The GJB6del(GJB6-D13S1830)mutation causes allele-specific loss of GJB2expression in cis[J].Biochemical and Biophysical Research Communications,2009,389:354.

16 Rodriguez-Paris J,Tamayo ML,Gelvez N,et al.Allele-specific impairment of GJB2expression by GJB6deletion del(GJB6-D13S1854)[J].PLoS One,2011,6:e21 665.

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陈垲钿宗凌周蔚刘敏姜鸿彦