Identification of Mutations in the CRB1, RPE65, RETGC1, AIPL1, and RPGRIP1 Genes in a Cohort of 38 Patients With Juvenile Retinitis Pigmentosa

Abstract

Abstract: : Purpose: To identify novel causative mutations in the CRB1, RPE65, RETGC1, and AIPL1, RPGRIP1 genes by a comprehensive screen of a cohort of patients with Leber congenital amaurosis (LCA) or autosomal recessive Retinitis Pigmentosa (ARRP) with early onset. Methods: Clinical examination of 38 patients included visual acuity measurements, funduscopy and ERG. Blood samples were drawn and DNA was extracted using standardized methods. DNA mutation analysis was carried out by Denaturing High Pressure Liquid Chromatography (DHPLC) analysis, followed by direct sequencing. Results: Mutations were found in CRB1 in (16%), RPE65 (11%), RETGC1 (11%), AIPL1 (3%), and RPGRIP1 (5%) of patients. We report two novel mutations (in RETGC1 and RPGRIP1) and a novel combination of two mutations in CBR1. In addition, we describe a RETGC1 mutation, previously implicated in LCA, in ARRP for the first time. Finally, we established the polymorphic nature of two previously decribed sequence changes in CRB1 en AIPL1. Conclusions: We detected two new mutations in RETGC1 and RPGRIP1 and found mutations in RETGC1 and CRB1 in both LCA and ARRP patients. Seven new polymorphic changes were also found. Our data, combined with those of the literature suggest that LCA and early onset ARRP are closely related and overlapping entities of juvenile RP.

Keywords: retinal degenerations: hereditary • genetics • retina