GENOTYPE & PHENOTYPE IN LEBER CONGENITAL AMAUROSIS & RELATED RETINAL DISORDERS

1996年和1997年发现了Leber先天性黑蒙症（LCA）、早发性视网膜色素变性（RP）和视锥-视杆细胞营养不良（CRD）的三种疾病基因。 每个基因都与LCA、RP或CRD有关。这些都是复发性遗传性疾病，导致视力障碍和失明的儿科患者。这三个基因是：1）CRX，参与视蛋白表达和感光细胞分化;在感光细胞中表达; 2）RetGC，视网膜鸟苷酸环化酶;也在感光细胞中表达;和3）RPE 65，在视网膜色素上皮中表达;可能是视觉周期中的异构酶。 这些基因很可能控制着人类视网膜的功能，可以通过适当的测试进行评估。具体目的：1）检测LCA、早期RP和CRD患者及其家族成员的CRX、RetGC和RPE 65基因突变。 2)使用视网膜电图（ERG），暗适应研究和反射视网膜密度测定来测试视网膜功能改变的假设。 3)检查基因型和视网膜表型（即视网膜功能参数）的显著关系。

Three disease genes for Leber Congenital Amaurosis (LCA), early onset Retinitis Pigmentosia (RP) and Cone-Rod Dystrophy (CRD) were discovered in 1996 and 1997. Each of the genes has been implicated in LCA, RP or CRD. These are recessively inherited disorders that lead to visual impairment and blindness of pediatric patients. The three genes are: 1) CRX, involved in opsin expression and photoreceptor differentiation; expressed in the photoreceptors; 2) RetGC, Retinal Guanylyl Cyclase; also expressed in the photoreceptors; and 3) RPE65, expressed in the retinal pigment epithelium; possibly the isomerase in the visual cycle. It is likely that these genes govern human retinal functions that can be evaluated by appropriate tests. Specific Aims: 1) Test patients with LCA, early RP, and CRD and family members for mutations of CRX, RetGC and RPE65 genes. 2) Use electroretinography (ERG), Dark Adaptation studies and Reflection Retinal Densitometry to test the hypothesis of altered retinal function. 3) Examine the genotypes and retinal phenotypes (that is, the parameters of retinal function) for significant relations.