SNPscan法用于新疆主要少数民族非综合征型聋患者GJB2基因突变筛查的研究

Screeing Using SNPscan Method for GJB2 Gene Mutation among Non-syndromic Deaf Patients of the Dominant Ethnic Minorities in Xinjiang

陈兴健;徐百成;陈迟;朱一鸣;刘晓雯;杨小龙;王艳莉;边盼盼;郭玉芬;

1:兰州大学第二医院耳鼻咽喉头颈外科

2:甘肃省人民医院

3:甘肃省卫生厅

摘要
目的分析新疆主要少数民族非综合征型聋(nonsydromic hearing loss,NSHL)患者GJB2基因突变的流行病学及突变特征。方法采集新疆维吾尔自治区四个主要少数民族565例(维吾尔族428例,回族41例,哈萨克族64例,柯尔克孜族32例)中重度至极重度感音神经性聋患者的外周静脉血,提取基因组DNA,应用SNPscan法对GJB2基因40个已知突变位点进行筛查,并进行统计学分析。结果维吾尔族、回族、哈萨克族和柯尔克孜族NSHL患者GJB2基因的致病突变位点的等位基因频率分别为10.16%(87/856)、15.85%(13/82)、10.16%(13/128)、1.56%(1/64),其中,回族最高,维吾尔族和哈萨克族次之,柯尔克孜族最低,差异有统计学意义(χ2=8.140,P=0.043);c.235delC仅在维吾尔族和回族NSHL患者中发现,等位基因频率分别为5.14%(44/856)和13.41%(11/82)。而c.35delG在维吾尔族、回族、哈萨克族、柯尔克孜族NSHL患者中均有发现,等位基因频率分别为3.15%(27/856)、1.21%(1/82)、8.59%(11/128)和1.56%(1/64)。结论新疆维吾尔族、回族、哈萨克族及柯尔克孜族非综合征型聋患者GJB2基因突变发生率均较高,c.235delC是新疆地区维吾尔族和回族NSHL患者的热点突变,c.35delG是维吾尔族、哈萨克族和柯尔克孜族NSHL患者的热点突变。
关键词
非综合征型聋;缝隙连接蛋白B2;新疆;少数民族;突变;单核苷酸多肽性
基金项目(Foundation):
作者
陈兴健;徐百成;陈迟;朱一鸣;刘晓雯;杨小龙;王艳莉;边盼盼;郭玉芬;
参考文献

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

2 Dalamón V,Lotersztein V,Béhèran A,et al.GJB2and GJB6genes:molecular study and identification of novel GJB2mutations in the hearing-impaired Argentinean population[J].Audiology and Neurotology,2009,15:194.

3 Kelley P,Harris D,Comer B,et al.Novel mutations in the connexin 26 gene(GJB2)that cause autosomal recessive(DFNB1)hearing loss[J].The American Journal of Human Genetics,1998,62:792.

4 Tekin M,Xia XJ,Erdenetungalag R,et al.GJB2mutations in Mongolia:complex alleles,low frequency,and reduced fitness of the deaf[J].Ann Hum Genet,2010,74:155.

5 Guo YF,Liu XW,Guan J,et al.GJB2,SLC26A4and mitochondrial DNA A1555G mutations in prelingual deafness in Northern Chinese subjects[J].Acta Oto-laryngologica,2008,128:297.

6 Ohtsuka A,Yuge I,Kimura S,et al.GJB2deafness gene shows a specific spectrum of mutations in Japan,including a frequent founder mutation[J].Hum Genet,2003,112:329.

7 Crawford A,Fassett RG,Geraghty DP,et al.Relationships between single nucleotide polymorphisms of antioxidant enzymes and disease[J].Gene,2012,501:89.

8 Dai P,Yu F,Han B,et al.The prevalence of the 235delC GJB2mutation in a Chinese deaf population[J].Genetics in Medicine,2007,9:283.

9 Abidi O,Boulouiz R,Nahili H,et al.GJB2(connexin 26)gene mutations in Moroccan patients with autosomal recessive non-syndromic hearing loss and carrier frequency of the common GJB2–35delG mutation[J].Int J Pediatr Otorhinolaryngol,2007,71:1 239.

10 满荣军,郭玉芬,刘晓雯,等.新疆少数民族和汉族聋哑学生GJB2基因和线粒体DNA 12SrRNA A1555G突变研究[J].中国耳鼻咽喉头颈外科,2009,16:190.

11 陈俞,赵娟,皮力东·库亚西,等.新疆不同民族耳聋人群耳聋基因常见突变的筛查[J].新疆医科大学学报,2011,8:850.

12 杜若甫.我国的人类群体遗传学研究[J].生物学通报,1997,32:9.

13 Kenneson A,Braun KVN,Boyle C.GJB2(connexin 26)variants and nonsyndromic sensorineural hearing loss:a HuGE review[J].Genetics in Medicine,2002,4:258.

14 Abe S,Usami SZ,Shinkawa H,et al.Prevalent connexin 26gene(GJB2)mutations in Japanese[J].J Med Genet,2000,37:41.

15 Dai P,Yu F,Han B,et al.GJB2mutation spectrum in 2063Chinese patients with nonsyndromic hearing impairment[J].J Transl Med,2009,7:1.

16 马建鹂,徐百成,边盼盼,等.中国西北地区回族非综合征型聋患者耳聋相关基因研究[J].听力学及言语疾病杂志,2013,21:451.

17 王国建,戴朴,韩东一,等.基因芯片技术在非综合征性耳聋快速基因诊断中的应用研究[J].中华耳科学杂志,2008,6:61.

18 Tang LL,Chen FY,Wang H,et al.Haplotype analysis of eight genes of the monoubiquitinated FANCD2–DNA damage–repair pathway in breast cancer patients[J].Cancer Epidemiology,2013,37:311.

19 Chen X,Li S,Yang Y,et al.Genome‐wide association study validation identifies novel loci for atherosclerotic cardiovascular disease[J].Journal of Thrombosis and Haemostasis,2012,10:1 508.