Clinical Features of Autosomal Dominant Retinitis Pigmentosa Associated With Mutation in the NRL Gene: Report of an Italian Family

Abstract

Abstract: : Purpose: To determine the phenotypic manifestation of autosomal dominant retinitis pigmentosa (ADRP) Italian family with a mutation in the NRL gene. Methods: Five ADRP patients from an ADRP family (mean age 32.4 + 13.3 years) underwent a complete ophthalmologic examination, including, best corrected visual acuity, Goldmann perimetry, fundus examination, electroretinography (ERG), optical coerence tomography (OCT) and scanning laser ophthalmoscopy (SLO). The DNA sequence of the coding exons of the NRL gene, were amplified by PCR in the proband and his relatives. Mutation screening was performed by direct sequencing on an ABI 377 sequencer. Results: Molecular analysis revealed a P51L mutation in the NRL gene in all affected members. The mean age at the onset of disease in the 5 ADRP patients was 1.4 years (+ 0.8 SD). Best corrected visual acuity varied from 0,8 to no light perception. Fundus examination showed a typical retinitis pigmentosa associated with macular dystrophy in 3 patients. In these patients the OCT examination demonstrated the presence of cystoid macular edema. In all patients, except one, we observed a peripapillary atrophy and 2 of the patients showed optic disc drusen at SLO autofluorescence. ERG testing revealed an undetectable scotopic and photopic response in all patients until our first observation at the mean age of 19 years. Conclusions: In this family the NRL P51L mutation is associated with a severe form of retinitis pigmentosa associated with cystoid macular edema and peripapillary chorioretinal atrophy. Comparison with published data on RP phenotypes associated with P51L mutation suggests that these two features if observed in several members of a family would be consistent with an underlying NRL gene mutation.

Keywords: retinitis • genetics • pathology: human