GJB2基因突变引起的显性遗传非综合征型耳聋家系研究

戴翔; 李隽; 胡晞江; 童静; 蔡文倩

doi:10.13201/j.issn.1001-1781.2016.24.009

GJB2基因突变引起的显性遗传非综合征型耳聋家系研究

- 1 武汉市妇女儿童医疗保健中心(武汉市儿童医院武汉市妇幼保健院)生殖医学实验室(武汉, 430016);
- 2 武汉市妇女儿童医疗保健中心(武汉市儿童医院武汉市妇幼保健院)耳鼻咽喉科
基金项目:
湖北省自然科学基金面上项目(No:2014CKB511)

武汉市卫计委科研项目(No:WX15C20)

武汉市青年科技晨光计划项目(No:200950431210)联合资助

详细信息

通讯作者: 李隽,E-mail:junlzeng@hotmail.com

中图分类号: R764.43

收稿日期: 2016-08-01

Autosomal dominant hearing loss resulting from mutation in the GJB2 gene:nonsyndromic presentation in a Chinese family

- 1 Reproduction Medicine Laboratory of Wuhan Medical and Health Center for Women and Children(Wuhan Children's Hospital, Wuhan Women and Children Care Hospital), Wuhan, 430016, China;
- 2 Department of Otolaryngology of Wuhan Medical and Health Center for Women and Children(Wuhan Children's Hospital, Wuhan Women and Children Care Hospital)

More Information

Corresponding author: LI Jun, E-mail: junlzeng@hotmail.com

Received Date: 01 August 2016

摘要

摘要: 目的:检测一显性遗传非综合征型耳聋家系GJB2、GJB3、GJB6、SLC26A4、线粒体12SrRNA和线粒体tRNA^Ser(UCN)等基因突变情况,探讨其基因型、表型和遗传学特征。方法:收集家系中先证者和部分亲属的临床资料,采集其外周血样本,并提取DNA。扩增GJB2、GJB3、GJB6、SLC26A4基因编码区和线粒体基因耳聋致病相关区域,并以直接测序法进行突变分析。结果:先证者和母亲均携带GJB2基因R75Q杂合突变,而其他检测基因未见致病突变。结论:GJB2基因R75Q突变引起先证者和母亲常染色体显性遗传非综合征型耳聋。R75Q能由亲代遗传至子代,基因检查的结果可为进一步生育指导提供帮助。
- 聋 /
- 连接蛋白 /
- GJB2 /
- 遗传
Abstract: Objective: To investigate the genotype, phenotype and genetic features. The mutations in GJB2, GJB3, GJB6, SLC26A4 genes, 12SrRNA and tRNASer(UCN) were tested in a Chinese family with autosomal dominant nonsyndromic hearing loss.Method: Blood samples and clinical data of the proband and her partial family members were collected. DNA was extracted from the blood samples. The GJB2, GJB3, GJB6, SLC26A4 genes, 12SrRNA and tRNASer(UCN) mutations were analyzed by polymerase chain reaction(PCR) and direct sequencing.Result: Heterozygous mutation of GJB2 R75Q was identified in the proband and her mother. No mutation of other testing genes was detected.Conclusion: The R75Q mutation of the GJB2 gene cause autosomal dominant nonsyndromic deafness in the proband and her mother. Children can inherit the R75Q mutation from their parents, so the results of gene testing will be helpful for further guidance of procreation.
- deafness /
- connexin /
- GJB2 /
- heredity

HTML全文

参考文献(15)

[1]	田勇泉,韩东一,迟放鲁,等.耳鼻咽喉头颈外科学[M].8版.北京:人民卫生出版社,2013:353-353.
[2]	YANG J J,WANG W H,LIN Y C,et al.Prospective variants screening of connexin genes in children with hearing impairment:genotype/phenotype correlation[J].Hum Genet,2010,128:303-313.
[3]	YANG X L,BAI-CHENG X,CHEN X J,et al.Common molecular etiology of patients with nonsyndromic hearing loss in Tibetan,Tu nationality,and Mongolian patients in the northwest of China[J].Acta Otolaryngol,2013,133:930-934.
[4]	ADHIKARY B,GHOSH S,PAUL S,et al.Spectrum and frequency of GJB2,GJB6 and SLC26A4 gene mutations among nonsyndromic hearing loss patients in eastern part of India[J].Gene,2015,573:239-245.
[5]	TANG X,ZHENG J,YING Z,et al.Mitochondrial tRNA(Ser(UCN))variants in 2651 Han Chinese subjects with hearing loss[J].Mitochondrion,2015,23:17-24.
[6]	BIRKENHAGER R,LUBLINGHOFF N,PRERA E,et al.Autosomal dominant prelingual hearing loss with palmoplantar keratoderma syndrome:Variability in clinical expression from mutations of R75W and R75Q in the GJB2 gene[J].Am J Med Genet A,2010,152A:1798-1802.
[7]	FELDMANN D,DENOYELLE F,BLONS H,et al.The GJB2 mutation R75Q can cause nonsyndromic hearing loss DFNA3 or hereditary palmoplantar keratoderma with deafness[J].Am J Med Genet A,2005,137:225-227.
[8]	JIANG S J,DI Z H,HUANG D,et al.R75Q de novo dominant mutation of GJB2 in a Chinese family with hearing loss and palmoplantar keratoderma[J].Int J Pediatr Otorhinolaryngol,2014,78:1461-1466.
[9]	PIAZZA V,BELTRAMELLO M,MENNITI M,et al.Functional analysis of R75Q mutation in the gene coding for Connexin 26identified in a family with nonsyndromic hearing loss[J].Clin Genet,2005,68:161-166.
[10]	LOSSA S,CHINETTI V,CORVINO V,et al.R75Q dominant mutation in GJB2 gene silenced by the in Cis recessive mutation c.35delG[J].Am J Med Genet A,2010,152A:2658-2660.
[11]	CHEN Y,DENG Y,BAO X,et al.Mechanism of the defect in gap-junctional communication by expression of a connexin 26mutant associated with dominant deafness[J].FASEB J,2005,19:1516-1518.
[12]	MINEKAWA A,ABE T,INOSHITA A,et al.Cochlear outer hair cells in a dominant-negative connexin26 mutant mouse preserve non-linear capacitance in spite of impaired distortion product otoacoustic emission[J].Neuroscience,2009,164:1312-1319.
[13]	ROUAN F,WHITE T W,BROWN N,et al.transdominant inhibition of connexin-43by mutant connexin-26:implications for dominant connexin disorders affecting epidermal differentiation[J].J Cell Sci,2001,114(Pt 11):2105-2113.
[14]	YUM S W,ZHANG J,SCHERER S S.Dominant connexin26 mutants associated with human hearing loss have trans-dominant effects on connexin30[J].Neurobiol Dis,2010,38:226-236.
[15]	PANDEY N,XAVIER D F,CHATTERJEE A,et al.Functional Analysis of a Novel Connexin30 Mutation in a Large Family with Hearing Loss,Pesplanus,Ichthyosis,Cutaneous Nodules,and Keratoderma[J].Ann Hum Genet,2016,80:11-19.