Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis.
Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis.
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DOI：
10.1186/1750-1172-6-21
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发表时间：
2011-05-11
影响因子：
3.7
通讯作者：
Denoyelle F
中科院分区：
文献类型：
--
作者：
Bonnet C;Grati M;Marlin S;Levilliers J;Hardelin JP;Parodi M;Niasme-Grare M;Zelenika D;Délépine M;Feldmann D;Jonard L;El-Amraoui A;Weil D;Delobel B;Vincent C;Dollfus H;Eliot MM;David A;Calais C;Vigneron J;Montaut-Verient B;Bonneau D;Dubin J;Thauvin C;Duvillard A;Francannet C;Mom T;Lacombe D;Duriez F;Drouin-Garraud V;Thuillier-Obstoy MF;Sigaudy S;Frances AM;Collignon P;Challe G;Couderc R;Lathrop M;Sahel JA;Weissenbach J;Petit C;Denoyelle F
Usher综合征（USH）是感音神经性耳聋与失明的结合。它以常染色体隐性方式遗传。早期诊断对于适应教育和患者管理选择以及遗传咨询至关重要。到目前为止，已经确定了三种临床亚型（USH1，USH2和USH3）的九个致病基因。目前的诊断策略利用基因分型微阵列，是基于以前报道的突变。本研究的目的是设计一种更准确的分子诊断工具。我们对54例USH患者（27例USH 1，21例USH 2和6例USH 3）的9个已知USH基因的366个编码外显子和侧翼区进行了测序。在39例患者（72%）中检测到双等位基因突变，在另外10例患者（18.5%）中检测到单等位基因突变。除了一个USH基因的双等位基因突变外，在7名患者（13%）中检测到另一个USH基因的可能致病突变，另一名患者在三个不同的USH基因中携带单等位基因突变。值得注意的是，USH3患者中没有一个在唯一已知的USH3基因中携带可检测的突变，而他们都携带USH2基因突变。最重要的是，目前使用的微阵列只能检测到我们发现的81种不同突变中的30种，其中39种（48%）是新的。基于这些结果，目前已知的USH基因的完整外显子测序代表了这种疾病的分子诊断的明确改进，这在基因治疗的角度是至关重要的。
Usher syndrome (USH) combines sensorineural deafness with blindness. It is inherited in an autosomal recessive mode. Early diagnosis is critical for adapted educational and patient management choices, and for genetic counseling. To date, nine causative genes have been identified for the three clinical subtypes (USH1, USH2 and USH3). Current diagnostic strategies make use of a genotyping microarray that is based on the previously reported mutations. The purpose of this study was to design a more accurate molecular diagnosis tool. We sequenced the 366 coding exons and flanking regions of the nine known USH genes, in 54 USH patients (27 USH1, 21 USH2 and 6 USH3). Biallelic mutations were detected in 39 patients (72%) and monoallelic mutations in an additional 10 patients (18.5%). In addition to biallelic mutations in one of the USH genes, presumably pathogenic mutations in another USH gene were detected in seven patients (13%), and another patient carried monoallelic mutations in three different USH genes. Notably, none of the USH3 patients carried detectable mutations in the only known USH3 gene, whereas they all carried mutations in USH2 genes. Most importantly, the currently used microarray would have detected only 30 of the 81 different mutations that we found, of which 39 (48%) were novel. Based on these results, complete exon sequencing of the currently known USH genes stands as a definite improvement for molecular diagnosis of this disease, which is of utmost importance in the perspective of gene therapy.
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影响因子：
9.8
作者：
Ahmed, ZM;Riazuddin, S;Wilcox, ER
通讯作者：
Wilcox, ER
影响因子：
3.4
作者：
Bharadwaj, AK;Kasztejna, JP;Dryja, TP
通讯作者：
Dryja, TP
影响因子：
3.5
作者：
Alagramam, KN;Yuan, HJ;Smith, RJH
通讯作者：
Smith, RJH
影响因子：
3.5
作者：
Ahmed, ZM;Riazuddin, S;Wilcox, ER
通讯作者：
Wilcox, ER
影响因子：
30.8
作者：
Bitner-Glindzicz, M;Lindley, KJ;Glaser, B
通讯作者：
Glaser, B