Mutations in the ABCA4 (ABCR) gene are the major cause of autosomal recessive cone-rod dystrophy
Mutations in the ABCA4 (ABCR) gene are the major cause of autosomal recessive cone-rod dystrophy
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DOI：
10.1086/303079
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发表时间：
2000-10-01
影响因子：
9.8
通讯作者：
Cremers, FPM
中科院分区：
文献类型：
--
作者：
Maugeri, A;Klevering, BJ;Cremers, FPM
感光细胞特异性ATP结合盒转运蛋白基因（ABCA 4;以前表示为“ABCR”）在大多数常染色体隐性（AR）Stargardt病（STGD 1）或眼底黄斑（FFM）患者中发生突变。此外，少数AR视网膜色素变性（RP）和AR视锥-视杆细胞营养不良（CRD）病例已被发现有ABCA 4突变。为了评估ABCA 4基因作为阿比特龙CRD病因的重要性，我们选择了5例AR CRD患者和15例孤立性CRD患者，均来自德国和荷兰。单链构象多态性分析和测序显示，20例患者中有13例（65%）存在19个ABCA 4突变。在6例患者中，在两个ABCA 4等位基因中均发现突变;在7例患者中，在一个等位基因中检测到突变。一个复杂的ABCA 4等位基因（L541 P; A1038 V）被发现专门在德国患者CRD;一个病人携带这个复杂的等位基因纯合子和其他五个复合杂合子。这些发现表明ABCA 4基因突变是AR CRD的主要原因。ABCA 4基因在STGD 1/FFM和AR CRD中的主要作用，以及该基因参与AR RP病例的比例尚不清楚，加强了ABCA 4基因突变可能是人类遗传性视网膜营养不良最常见原因的观点。
The photoreceptor cell-specific ATP-binding cassette transporter gene (ABCA4; previously denoted "ABCR") is mutated in most patients with autosomal recessive (AR) Stargardt disease (STGD1) or fundus flavimaculatus (FFM). In addition, a few cases with AR retinitis pigmentosa (RP) and AR cone-rod dystrophy (CRD) have been found to have ABCA4 mutations. To evaluate the importance of the ABCA4 gene as a cause of Abi CRD, we selected 5 patients with AR CRD and 15 patients with isolated CRD, all from Germany and The Netherlands. Single-strand conformation-polymorphism analysis and sequencing revealed 19 ABCA4 mutations in 13 (65%) of 20 patients. In six patients, mutations were identified in both ABCA4 alleles; in seven patients, mutations were detected in one allele. One complex ABCA4 allele (L541P;A1038V) was found exclusively in German patients with CRD; one patient carried this complex allele homozygously and five others were compound heterozygous. These findings suggest that mutations in the ABCA4 gene are the major cause of AR CRD. A primary role of the ABCA4 gene in STGD1/FFM and AR CRD, together with the gene's involvement in an as-yet-unknown proportion of cases with AR RP, strengthens the idea that mutations in the ABCA4 gene could be the most frequent cause of inherited retinal dystrophy in humans.