Description of the Natural History of Autosomal Dominant Retinitis Pigmentosa Caused by an Arg135Leu Mutation in Rhodopsin in a Nine Generation Family

Abstract

Abstract: : Purpose: To study the natural history of a large family with autosomal dominant retinitis pigmentosa (ADRP) and to correlate their phenotypic characteristics with the specific mutation responsible for the disease. Methods: A natural history study of a nine generation family with ADRP. 24 affected subjects from age 9 to 64 years were examined. Goldman visual fields, full field electroretinography (ERG) and standard ophthalmic exams with photography were performed. Goldman visual fields were converted to solid angle using previously reported methods. Molecular analysis was conducted using single-strand conformational polymorphism (SSCP) and polymerase chain reaction (PCR) techniques for the rhodopsin gene. Finally, the solid angle I4e isopter of this family was compared to two other populations of patients with Pro23His and Pro347Ala rhodopsin mutations. Results: An Arg135Leu mutation in the rhodopsin gene was identified in affected family members. Affected family members maintained central visual acuity of 20/40 or better through their third to fourth decades of life. Full field ERG was performed on 12 patients and all subjects were uniformly non-recordable for all studies using ISCEV standard testing. The youngest patient tested was 11 years of age. Six out of seven patients under age 20 demonstrated diffuse yellow white dots with minimal bone spicules. The one patient without yellow white dots had minimal associated fundus findings of RP. 11 of 17 patients over the age 20 either showed evidence of cataract or had undergone cataract extraction. Affected family members lost the II4e isopter by the fifth decade of life and the V4e isopter by the sixth decade of life. By comparison with known populations with Pro23His and Pro347Ala mutations in rhodopsin, the loss of the I4e solid angle is more severe in this family. Conclusions: The visual field and visual acuity course of ADRP caused by and Arg135Leu mutation in rhodopsin was described. This data also demonstrated that patients with this mutation have a more severe disease course than patients with ADRP caused by Pro23His and Pro347Ala mutations in rhodopsin.

Keywords: retinal degenerations: hereditary • clinical (human) or epidemiologic studies: nat • degenerations/dystrophies