Mutation analysis of 3 genes in patients with leber congenital amaurosis

Objective: To assess the frequency of mutations in the CRX, GUCY2D, and RPE 65 genes in patients with Leber congenital amaurosis (LCA). Patients: One hundred seventy-six probands with a clinical diagnosis of LCA were from 9 countries, with the largest subgroup being 39 probands from In dia. Methods: Samples were screened with single-strand conformation polymorphism analysis followed by DNA sequencing of 3 genes (CRX, GUCY2D, and RPE65) kn own to be associated with LCA. Results: Of the 176 probands, 28 (15.9%) harbored possible disease-causing mutations. The relative contribution of each gene to the total number of mu tations was as follows: CRX, 2.8%; GUCY2D, 6.3%; and RPE65, 6.8%. No patien ts who harbored mutations in these genes had associated systemic abnormalit ies. Molecular diagnosis allowed definitive genetic counseling in a family affected with Best disease and LCA. Conclusions: Molecular diagnosis may be of benefit to patients affected wit h LCA. The relative paucity of mutations found in this study suggests that more LCA-associated genes remain to be discovered. Clinical Relevance: Molecular diagnosis can confirm and clarify the diagnos is of LCA. As genotype. data accumulate, clinical phenotypes associated wit h specific mutations will be established. This will facilitate the counseli ng of patients on their visual prognosis and the likelihood of associated s ystemic anomalies.