Dharmaraj S R, Silva E R, Pina A L, Li Y Y, Yang J M, Carter C R, Loyer M K, El-Hilali H K, Traboulsi E K, Sundin O K, Zhu D K, Koenekoop R K, Maumenee I H
Wilmer Eye Institute, The Johns Hopkins Center for Hereditary Eye Diseases, Baltimore, Maryland, USA.
Ophthalmic Genet. 2000 Sep;21(3):135-50.
Leber congenital amaurosis (LCA, MIM 204001) is a clinically and genetically heterogeneous retinal disorder characterized by severe visual loss from birth, nystagmus, poor pupillary reflexes, retinal pigmentary or atrophic changes, and a markedly diminished electroretinogram (ERG).
To examine 100 consecutive patients with LCA in order to assess the relative burden of the three known genes involved in LCA, namely retinal guanylyl cyclase (GUCY2D), retinal pigment epithelium protein ( RPE65), and the cone-rod homeobox (CRX), and to define their clinical correlates.
Mutational analysis and detailed clinical examinations were performed in patients diagnosed with LCA at the Johns Hopkins Center for Hereditary Eye Diseases and the Montreal Children's Hospital.
Mutations were identified in 11% of our patients: GUCY2D mutations accounted for 6%, while RPE65 and CRX gene mutations accounted for 3% and 2%, respectively. The clinical presentation was variable; however, the visual evolution in patients with mutations in GUCY2D and CRX remained stable, while individuals with mutations in the RPE65 gene showed progressive visual loss.
This study suggests that molecular diagnosis of Leber congenital amaurosis could provide important information concerning prognosis and course of treatment.
莱伯先天性黑蒙（LCA，MIM 204001）是一种临床和遗传异质性视网膜疾病，其特征为出生时即有严重视力丧失、眼球震颤、瞳孔反射不良、视网膜色素沉着或萎缩性改变，以及视网膜电图（ERG）明显减弱。
对100例连续的LCA患者进行检查，以评估参与LCA的三个已知基因，即视网膜鸟苷酸环化酶（GUCY2D）、视网膜色素上皮蛋白（RPE65）和视锥-视杆同源框（CRX）的相对负担，并确定它们的临床相关性。
在约翰霍普金斯遗传性眼病中心和蒙特利尔儿童医院对诊断为LCA的患者进行突变分析和详细的临床检查。
在我们的患者中，11%发现了突变：GUCY2D突变占6%，而RPE65和CRX基因突变分别占3%和2%。临床表现各不相同；然而，GUCY2D和CRX突变患者的视力进展保持稳定，而RPE65基因突变的个体则表现出进行性视力丧失。
本研究表明，莱伯先天性黑蒙的分子诊断可为预后和治疗过程提供重要信息。
