GENOTYPE & PHENOTYPE IN LEBER CONGENITAL AMAUROSIS & RELATED RETINAL DISORDERS

Leber先天性黑色素沉着症(LCA)、早发性视网膜色素变性(RP)和视锥-杆营养不良症(CRD)的三个致病基因分别于1996年和1997年被发现。每个基因都与LCA、RP或CRD有关。这些都是隐性遗传性疾病，会导致儿童患者视力受损和失明。这三个基因是：1)CRX，参与视蛋白的表达和光感受器的分化，在光感受器中表达；2)视网膜鸟苷酸环化酶，也在光感受器中表达；3)RPE65，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、CRD患者及家系成员CRX、RetGC和RPE65基因突变。2)应用视网膜电流图(ERG)、暗适应研究和反射式视网膜密度计对视网膜功能改变的假说进行验证。3)检查基因类型和视网膜表型(即视网膜功能的参数)是否有显著关系。

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.