Homozygous deletion related to Alu repeats in RLBP1 causes retinitis punctata albescens
Homozygous deletion related to Alu repeats in RLBP1 causes retinitis punctata albescens
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DOI：
10.1167/iovs.05-1488
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发表时间：
2006-11-01
影响因子：
4.4
通讯作者：
Hamel, Christian P.
中科院分区：
文献类型：
--
作者：
Humbert, Ghyslaine;Delettre, Cecile;Hamel, Christian P.
目的。斑点状白化视网膜营养不良是一种罕见的常染色体隐性(和罕见显性)视网膜营养不良，以早发性严重夜盲和眼底微小点状白色沉积为特征。RPA主要与RLBP1的突变有关，偶尔也与Rho、RDS和RDH5的突变有关。本研究在典型RPA患者中寻找编码视黄醇结合蛋白CRALBP的RLBP1基因突变。方法临床检查包括眼底镜检查、视野检查、视网膜电信号记录和适应性检查。对RLBP1基因的7个编码外显子(3-9)和ABDH2基因的第15个(最后)外显子进行了聚合酶链式反应(PCR)扩增和测序。结果：这项研究涉及一位24岁的摩洛哥患者，他患有典型的RPA，父母是近亲。他携带一个7.36kb的纯合子缺失，包括RLBP1的最后3个外显子(7、8和9)以及RLBP1和位于RLBP1下游的ABHD2之间的部分基因间隔区。这一缺失取消了CRALBP的视网膜结合部位。RLBP1内含子6中缺失的端粒断裂点嵌入在Alu元件中，而着丝粒断裂点(位于基因间隔区)位于两个方向相反的Alu元件之间。结论由于RLBP1中Alu元件的密度很高，当一个或两个等位基因缺乏点突变时，如RPA或斑点状视网膜营养不良，应系统地寻找该基因的缺失。
PURPOSE. Retinitis punctata albescens (RPA) is an infrequently occurring form of autosomal recessive (and rarely dominant) retinal dystrophy featuring early-onset severe night blindness and tiny, dotlike, white deposits in the fundus. RPA is associated mostly with mutations in RLBP1 and occasionally in RHO, RDS, and RDH5. In this study, mutations were sought in RLBP1, which encodes the retinol binding protein CRALBP in patients with typical RPA.METHODS. Clinical investigation included funduscopy, visual field testing, electroretinogram recording, and adaptometry. The 7 coding exons (3 - 9) of RLBP1 and the 15th (last) exon of ABDH2 were PCR amplified and sequenced. Long-distance PCR and cloning of genomic DNA were performed to characterize the deletion.RESULTS. The study involved a 24-year-old Moroccan patient with typical RPA, born of first-cousin parents. He carried a 7.36-kb homozygous deletion encompassing the last 3 exons of RLBP1 (7, 8, and 9) and part of the intergenic region between RLBP1 and ABHD2, which lies downstream of RLBP1. This deletion abolishes the retinal binding site of CRALBP. The telomeric breakpoint of the deletion (in RLBP1 intron 6) is embedded in an Alu element, whereas the centromeric breakpoint (in the intergenic region) lies between two Alu elements placed in the opposite orientation.CONCLUSIONS. Because of the high density of Alu elements in RLBP1, a systematic search should be made for deletions in this gene when one or both alleles lack point mutations, in the case of RPA or flecked retinal dystrophy.