Autosomal dominant progressive sensorineural hearing loss due to a novel mutation in the KCNQ4 gene.
Autosomal dominant progressive sensorineural hearing loss due to a novel mutation in the KCNQ4 gene.
复制标题
DOI：
10.1001/archoto.2010.234
复制
发表时间：
2011-01
影响因子：
--
通讯作者：
Lesperance, Marci M.
中科院分区：
文献类型：
--
作者：
Arnett, Jameson;Emery, Sarah B.;Kim, Theresa B.;Boerst, Angelique K.;Lee, Kwanghyuk;Leal, Suzanne M.;Lesperance, Marci M.
目的：鉴定常染色体显性遗传性进行性感音神经性耳聋一家系的遗传病因。前瞻分子遗传学研究。学术基因研究实验室。一个显性进行性非综合征性感音神经性耳聋家族的17名成员：9名患者，6名未受影响的患者，以及2名配偶。来自问卷调查、访谈、系列听力图和医疗记录的临床数据；来自全基因组连锁分析和候选基因突变分析的基因数据。症状、发病年龄、系列测听数据，以及是否存在与耳聋相关的突变。该家系中的患者表现为常染色体显性遗传性非综合征高频进行性感音神经性聋，发病年龄从1岁到21岁不等。单核苷酸多态的全基因组连锁分析得到了与染色体1p34-p36上18.9-Mb区域连锁的证据，多点对数优势分数为3.6。这个区间包含一个已知的耳聋基因KCNQ4，它是DNFA2耳聋的基础。对KCNQ4的14个编码外显子和内含子-外显子连接进行测序，发现一个新的杂合性错义突变c.859G>；C，p.Gly287Arg。该突变破坏了磷酸结合环的高度保守的GYG基序(甘氨酸-酪氨酸-甘氨酸)，该基序被认为是维持孔结构和功能的关键。所有274名对照均为阴性突变。常染色体显性遗传性高频听力损失在遗传上是异质性的，连锁分析是在更大的家庭中识别病因的有效手段。这个家族中的耳聋是由KCNQ4的一个新突变引起的。
To identify the genetic etiology in a family with autosomal dominant progressive sensorineural hearing loss. Prospective molecular genetic research study. Academic genetic research laboratory. Seventeen members of a family with dominant progressive nonsyndromic sensorineural hearing loss: 9 affected, 6 unaffected, and 2 spouses. Clinical data from questionnaires, interviews, serial audiograms, and medical records; genetic data from genome-wide linkage analysis and candidate gene mutation analysis. Symptoms, age at onset, serial audiometric data, and the presence or absence of a deafness-associated mutation. Affected individuals in this family presented with autosomal dominant nonsyndromic high-frequency progressive sensorineural hearing loss, with age at onset ranging from 1 to 21 years. Genome-wide linkage analysis of single-nucleotide polymorphisms yielded evidence of linkage to an 18.9-Mb region on chromosome 1p34–p36, with a multipoint logarithm of odds score of 3.6. This interval contains a known deafness gene, KCNQ4, which underlies DNFA2 deafness. Sequencing of the 14 coding exons and intron-exon junctions of KCNQ4 revealed a novel heterozygous missense mutation, c.859G>C, p.Gly287Arg. The mutation disrupts the highly conserved GYG motif (glycine-tyrosine-glycine) of the phosphate- binding loop, hypothesized to be critical in maintaining pore structure and function. All 274 controls were negative for the mutation. Autosomal dominant high-frequency hearing loss is genetically heterogeneous, and linkage analysis is an efficient means of identifying the etiology in larger families. Deafness in this family is caused by a novel mutation in KCNQ4.
登录
查看更多内容
影响因子：
64.8
作者：
Frazer, Kelly A.;Ballinger, Dennis G.;Cox, David R.;Hinds, David A.;Stuve, Laura L.;Gibbs, Richard A.;Belmont, John W.;Boudreau, Andrew;Hardenbol, Paul;Leal, Suzanne M.;Pasternak, Shiran;Wheeler, David A.;Willis, Thomas D.;Yu, Fuli;Yang, Huanming;Zeng, Changqing;Gao, Yang;Hu, Haoran;Hu, Weitao;Li, Chaohua;Lin, Wei;Liu, Siqi;Pan, Hao;Tang, Xiaoli;Wang, Jian;Wang, Wei;Yu, Jun;Zhang, Bo;Zhang, Qingrun;Zhao, Hongbin;Zhao, Hui;Zhou, Jun;Gabriel, Stacey B.;Barry, Rachel;Blumenstiel, Brendan;Camargo, Amy;Defelice, Matthew;Faggart, Maura;Goyette, Mary;Gupta, Supriya;Moore, Jamie;Nguyen, Huy;Onofrio, Robert C.;Parkin, Melissa;Roy, Jessica;Stahl, Erich;Winchester, Ellen;Ziaugra, Liuda;Altshuler, David;Shen, Yan;Yao, Zhijian;Huang, Wei;Chu, Xun;He, Yungang;Jin, Li;Liu, Yangfan;Shen, Yayun;Sun, Weiwei;Wang, Haifeng;Wang, Yi;Wang, Ying;Xiong, Xiaoyan;Xu, Liang;Waye, Mary M. Y.;Tsui, Stephen K. W.;Wong, J. Tze-Fei;Galver, Luana M.;Fan, Jian-Bing;Gunderson, Kevin;Murray, Sarah S.;Oliphant, Arnold R.;Chee, Mark S.;Montpetit, Alexandre;Chagnon, Fanny;Ferretti, Vincent;Leboeuf, Martin;Olivier, Jean-Franccois;Phillips, Michael S.;Roumy, Stephanie;Sallee, Clementine;Verner, Andrei;Hudson, Thomas J.;Kwok, Pui-Yan;Cai, Dongmei;Koboldt, Daniel C.;Miller, Raymond D.;Pawlikowska, Ludmila;Taillon-Miller, Patricia;Xiao, Ming;Tsui, Lap-Chee;Mak, William;Song, You Qiang;Tam, Paul K. H.;Nakamura, Yusuke;Kawaguchi, Takahisa;Kitamoto, Takuya;Morizono, Takashi;Nagashima, Atsushi;Ohnishi, Yozo;Sekine, Akihiro;Tanaka, Toshihiro;Tsunoda, Tatsuhiko;Deloukas, Panos;Bird, Christine P.;Delgado, Marcos;Dermitzakis, Emmanouil T.;Gwilliam, Rhian;Hunt, Sarah;Morrison, Jonathan;Powell, Don;Stranger, Barbara E.;Whittaker, Pamela;Bentley, David R.;Daly, Mark J.;de Bakker, Paul I. W.;Barrett, Jeff;Chretien, Yves R.;Maller, Julian;McCarroll, Steve;Patterson, Nick;Pe'er, Itsik;Price, Alkes;Purcell, Shaun;Richter, Daniel J.;Sabeti, Pardis;Saxena, Richa;Schaffner, Stephen F.;Sham, Pak C.;Varilly, Patrick;Altshuler, David;Stein, Lincoln D.;Krishnan, Lalitha;Smith, Albert Vernon;Tello-Ruiz, Marcela K.;Thorisson, Gudmundur A.;Chakravarti, Aravinda;Chen, Peter E.;Cutler, David J.;Kashuk, Carl S.;Lin, Shin;Abecasis, Goncalo R.;Guan, Weihua;Li, Yun;Munro, Heather M.;Qin, Zhaohui Steve;Thomas, Daryl J.;McVean, Gilean;Auton, Adam;Bottolo, Leonardo;Cardin, Niall;Eyheramendy, Susana;Freeman, Colin;Marchini, Jonathan;Myers, Simon;Spencer, Chris;Stephens, Matthew;Donnelly, Peter;Cardon, Lon R.;Clarke, Geraldine;Evans, David M.;Morris, Andrew P.;Weir, Bruce S.;Tsunoda, Tatsuhiko;Johnson, Todd A.;Mullikin, James C.;Sherry, Stephen T.;Feolo, Michael;Skol, Andrew
通讯作者：
Skol, Andrew
影响因子：
9.8
作者：
O'Connell, JR;Weeks, DE
通讯作者：
Weeks, DE
影响因子：
30.8
作者：
Abecasis, GR;Cherny, SS;Cardon, LR
通讯作者：
Cardon, LR
影响因子：
64.5
作者：
Kubisch, C;Schroeder, BC;Jentsch, TJ
通讯作者：
Jentsch, TJ
影响因子：
3.5
作者：
Wollnik, B;Schroeder, BC;Jentsch, TJ
通讯作者：
Jentsch, TJ