Carrier re-sequencing reveals rare but benign variants in recessive deafness genes.
Carrier re-sequencing reveals rare but benign variants in recessive deafness genes.
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载体重测序揭示了隐性耳聋基因中罕见但良性的变异
DOI：
10.1038/s41598-017-10099-2
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发表时间：
2017-09-12
影响因子：
4.6
通讯作者：
Wu H
中科院分区：
文献类型：
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作者：
He L;Pang X;Chen P;Wang X;Yang T;Wu H
对于隐性孟德尔疾病，在没有扩展谱系和/或功能分析的情况下，确定已知致病基因中罕见的非同义变体的致病性可能具有挑战性。在这项研究中，我们建议建立一个数据库的罕见，但良性变异的隐性耳聋基因的系统载体重新测序。作为一项初步研究，从18名耳聋先证者的未受影响的家庭成员中确定了30名耳聋致病变异的杂合子携带者。通过靶向下一代测序或桑格测序，对这些载体中相应基因的整个编码区进行重新测序。在听力正常的携带者中共发现了32种非同义变异，与致病变异相反，因此被归类为良性。其中有五种罕见的（次要等位基因频率小于0.005）先前未定义、有争议或甚至错误分类功能的变体：p.A434T SLC 26 A4中的p.R266Q（c.797G> A），MYO 15 A中的p.K96Q（c.286A> C），GJB 2中的p.T123N（c.368C> A）和CDH 23中的p.V1299I（c.797G> A）。我们的研究结果表明，大规模的载体重新测序可能是必要的，以建立一个罕见的，但良性的致病基因变异的数据库，以减少隐性孟德尔疾病的假阳性遗传诊断。
For recessive Mendelian disorders, determining the pathogenicity of rare, non-synonymous variants in known causative genes can be challenging without expanded pedigrees and/or functional analysis. In this study, we proposed to establish a database of rare but benign variants in recessive deafness genes by systematic carrier re-sequencing. As a pilot study, 30 heterozygous carriers of pathogenic variants for deafness were identified from unaffected family members of 18 deaf probands. The entire coding regions of the corresponding genes were re-sequenced in those carriers by targeted next-generation sequencing or Sanger sequencing. A total of 32 non-synonymous variants were identified in the normal-hearing carriersin transwith the pathogenic variant and therefore were classified as benign. Among them were five rare (minor allele frequencies less than 0.005) variants that had previously undefined, disputable or even misclassified function: p.A434T (c.1300 G > A) inSLC26A4, p.R266Q (c.797 G > A) inLOXHD1, p.K96Q (c.286 A > C) inMYO15A, p.T123N (c.368 C > A) inGJB2and p.V1299I (c.797 G > A) inCDH23. Our results suggested that large scale carrier re-sequencing may be warranted to establish a database of rare but benign variants in causative genes in order to reduce false positive genetic diagnosis of recessive Mendelian disorders.
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针对患有非综合征性感音神经性听力损失的维吾尔族家庭进行下一代测序。
影响因子：
3.7
作者：
Chen Y;Wang Z;Wang Z;Chen D;Chai Y;Pang X;Sun L;Wang X;Yang T;Wu H
通讯作者：
Wu H
影响因子：
4
作者：
Le Quesne Stabej P;Saihan Z;Rangesh N;Steele-Stallard HB;Ambrose J;Coffey A;Emmerson J;Haralambous E;Hughes Y;Steel KP;Luxon LM;Webster AR;Bitner-Glindzicz M
通讯作者：
Bitner-Glindzicz M
影响因子：
3.7
作者：
Mutai H;Suzuki N;Shimizu A;Torii C;Namba K;Morimoto N;Kudoh J;Kaga K;Kosaki K;Matsunaga T
通讯作者：
Matsunaga T
影响因子：
9.8
作者：
Shearer, A. Eliot;Eppsteiner, Robert W.;Smith, Richard J. H.
通讯作者：
Smith, Richard J. H.
在听力受损的个体中，有针对性的聋哑基因的下一代测序揭示了信息性突变。
DOI：
10.1038/gim.2014.65
发表时间：
2014-12
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
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作者：
通讯作者：
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