High frequency of CRB1 mutations as cause of Early-Onset Retinal Dystrophies in the Spanish population.
High frequency of CRB1 mutations as cause of Early-Onset Retinal Dystrophies in the Spanish population.
复制标题
DOI：
10.1186/1750-1172-8-20
复制
发表时间：
2013-02-05
影响因子：
3.7
通讯作者：
Ayuso C
中科院分区：
文献类型：
--
作者：
Corton M;Tatu SD;Avila-Fernandez A;Vallespín E;Tapias I;Cantalapiedra D;Blanco-Kelly F;Riveiro-Alvarez R;Bernal S;García-Sandoval B;Baiget M;Ayuso C
CRB 1突变被报道为具有不同表型表现的严重先天性和早发性视网膜营养不良（EORD）的原因，包括Leber先天性黑蒙（LCA）、视网膜色素变性（RP）和视锥-视杆营养不良。仅在少数队列中进行了全基因的综合突变扫描，主要是在LCA患者中。在这里，我们的目标是通过在一个大队列的LCA和EORP病例中广泛筛查CRB 1突变，调查西班牙人群中CRB 1突变的真实的患病率。本报告整合了我们西班牙LCA和早发性RP（EORP）队列中CRB 1缺陷先前研究的数据，以及对整个基因进行全面突变筛查的新发现。所使用的分子工具包括突变基因分型阵列、全基因组纯合性作图、优化的高分辨率解链（HRM）分析和桑格测序。一个大型的临床特征良好的队列研究了404例西班牙病例，其中114例患有LCA和290例EORP。这项研究表明，11%的西班牙患者携带CRB 1突变，范围从9%的EORP到14%的LCA病例。超过四分之三的突变是在西班牙队列中首次描述的，其中13个是未报告的新变体，13个在我们以前的研究中已经报道过。这项工作提供了西班牙EORD患者中广泛的CRB 1突变，并证明CRB 1在西班牙EORP患者中作为致病基因的主要作用。值得注意的是，到目前为止，仅在我们的队列中发现了高比例的私人突变。据我们所知，这项研究代表了西班牙LCA和EORP队列中最完整的CRB 1突变筛查，使我们能够建立基因特异性频率，并提供西班牙人群中广泛的CRB 1突变。
CRB1 mutations are reported as cause of severe congenital and early-onset retinal dystrophies (EORD) with different phenotypic manifestations, including Leber congenital amaurosis (LCA), retinitis pigmentosa (RP) and cone-rod dystrophies. Comprehensive mutational scanning of the whole gene has been only performed in few cohorts, mainly in LCA patients. Here, we aimed investigating the real prevalence of CRB1 mutations in the Spanish population by extensive screening of CRB1 mutations in a large cohort of LCA and EORP cases. This report integrates data from previous studies on CRB1 defects in our Spanish cohort of LCA and early-onset RP (EORP) with new findings from a comprehensive mutational screening of the whole gene. The molecular tools used include mutation genotyping arrays, whole-genome homozygosity mapping, an optimized high-resolution melting (HRM) analysis and Sanger sequencing. A large clinically well-characterized cohort of 404 Spanish cases was studied, 114 of which suffered from LCA and 290 from EORP. This study reveals that 11% of Spanish patients carried mutations in CRB1, ranging from 9% of EORP to 14% of LCA cases. More than three quarters of the mutations identified herein have been first described in this Spanish cohort, 13 of them are unreported new variants and 13 had been previously reported in our previous studies. This work provides a wide spectrum of CRB1 mutations in the Spanish EORD patients and evidences the major role of CRB1 as causal gene in the Spanish EORP patients. It is noteworthy that a high rate of private mutations only described in our cohort has been found so far. To our knowledge, this study represents the most complete mutational screening of CRB1 in a Spanish LCA and EORP cohort, allowing us to establish gene-specific frequencies and to provide a wide spectrum of CRB1 mutations in the Spanish population.
登录
查看更多内容
影响因子：
1.2
作者：
Lotery, A J;Malik, A;Stone, E M
通讯作者：
Stone, E M
影响因子：
2.6
作者：
den Hollander, AI;Ghiani, M;Broccoli, V
通讯作者：
Broccoli, V
影响因子：
--
作者：
Lotery, AJ;Jacobson, SG;Stone, EM
通讯作者：
Stone, EM
影响因子：
4.1
作者：
Henderson, Robert H.;Mackay, Donna S.;Moore, Anthony T.
通讯作者：
Moore, Anthony T.
影响因子：
64.8
作者：
Pellikka, M;Tanentzapf, G;Tepass, U
通讯作者：
Tepass, U