Cremers Frans P M, van den Hurk José A J M, den Hollander Anneke I
Department of Human Genetics, University Medical Center Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Hum Mol Genet. 2002 May 15;11(10):1169-76. doi: 10.1093/hmg/11.10.1169.
Leber congenital amaurosis (LCA) is the most common inherited cause of blindness in childhood and is characterised by a severe retinal dystrophy before the age of one year. Six genes have been identified that together account for approximately half of all LCA patients. These genes are expressed preferentially in the retina or the retinal pigment epithelium. Their putative functions are quite diverse and include retinal embryonic development (CRX), photoreceptor cell structure (CRB1), phototransduction (GUCY2D), protein trafficking (AIPL1, RPGRIP1), and vitamin A metabolism (RPE65). The molecular data for CRB1 and RPE65 support previous hypotheses that LCA can represent the severe end of a spectrum of retinal dystrophies. Given the diverse mechanisms underlying the disease, future therapies of LCA may need to be tailored to certain genetically defined subgroups. Based on experimental evidence in mice and dogs, patients with disturbed retinal metabolism of vitamin A through a mutation in the RPE65 gene will likely be the first candidates for future therapeutic trials.
莱伯先天性黑蒙（LCA）是儿童期最常见的遗传性失明病因，其特征是在一岁前出现严重的视网膜营养不良。已鉴定出六个基因，它们共同构成了约一半的LCA患者病因。这些基因在视网膜或视网膜色素上皮中优先表达。它们的推定功能相当多样，包括视网膜胚胎发育（CRX）、光感受器细胞结构（CRB1）、光转导（GUCY2D）、蛋白质运输（AIPL1、RPGRIP1）和维生素A代谢（RPE65）。CRB1和RPE65的分子数据支持了先前的假设，即LCA可能代表视网膜营养不良谱系的严重末端。鉴于该疾病背后的机制多样，未来LCA的治疗可能需要针对某些基因定义的亚组进行定制。基于小鼠和犬类的实验证据，因RPE65基因突变导致维生素A视网膜代谢紊乱的患者很可能是未来治疗试验的首批候选对象。
