EYS Is a Major Gene for Rod-cone Dystrophies in France
EYS Is a Major Gene for Rod-cone Dystrophies in France
复制标题
DOI：
10.1002/humu.21249
复制
发表时间：
2010-05-01
期刊：
影响因子：
3.9
通讯作者：
Zeitz, Christina
中科院分区：
文献类型：
--
作者：
Audo, Isabelle;Sahel, Jose-Alain;Zeitz, Christina
常染色体隐性视网膜色素变性（arRP）最近与新基因EYS的突变有关，EYS跨越2 Mb，使其成为人眼中表达的最大已知基因。本研究的目的是在239例散发性和arRP法国病例的临床特征良好的队列中确定EYS突变的患病率和性质。在186名先前通过应用微阵列技术排除已知突变的受试者中进行EYS直接测序。我们在总共29名患者中鉴定了EYS的新突变：其中15个突变被预测会产生提前终止密码子，2个代表外显子缺失。此外，检测到20个错义、沉默或剪接位点突变。患者显示纯合或复合杂合突变，在某些情况下，只有一个单一的突变。大多数患者表现为RP的经典体征，中心视力和视野相对保留，直到疾病的后期。1例患者显示视网膜下部疾病占优势，提示潜在的表型变异性。与患病率为12%或更多，我们提供的证据表明，EYS是一个主要的基因RP在法国和可能在其他地方。(C)2010 Wiley-Liss，Inc.
Autosomal-recessive retinitis pigmentosa (arRP) was recently associated with mutations in a novel gene EYS, spanning over 2 Mb, making it the largest known gene expressed in the human eye. The purpose of this study was to establish the prevalence and nature of EYS mutations in a clinically well-characterized cohort of 239 sporadic and arRP French cases. Direct sequencing of EYS was performed in 186 subjects for whom known mutations had previously been excluded by applying microarray technology. We mostly identified novel mutations in EYS in a total of 29 patients: Fifteen of the mutations were predicted to create premature stop codons and two represent exonic deletions. In addition, twenty missense, silent or splice-site mutations were detected. Patients revealed homozygous or compound heterozygous mutations and in some cases, only a single mutation. Most patients showed classical signs of RP with relatively preserved central vision and visual field until late in the course of the disorder. One patient showed predominance of the disease in the inferior part of the retina suggesting potential phenotypic variability. With a prevalence of 12% or more we provide evidence that EYS is a major gene for RP in France and probably elsewhere. (C) 2010 Wiley-Liss, Inc.