The Phenotype of a French Canadian Retinitis Pigmentosa Pedigree Linked to RP31, a Novel Dominant RP Locus

Abstract

Purpose: : To describe the phenotype of a large French–Canadian autosomal dominant retinitis pigmentosa (ADRP) family linked to the novel locus RP31 and compare the disease patterns to the 12 currently known ADRP phenotypes.

Methods: : Best–corrected visual acuities, slit lamp biomicroscopy, dilated fundus examinations, electroretinograms (ISCEV standards) and kinetic perimetry (Goldmann) were performed on all 17 affected and 10 unaffected members.

Results: : We identified a three generation family with ADRP in 17 members. Age at time of examination ranged from 8–64 years. Onset of symptoms (nyctalopia) ranged from 10–50 years and differed between the generations, while three affected patients were asymptomatic. Visual acuities ranged from 20/20 to count fingers and were well maintained in most patients as 16/17 had better than 20/40 and 11/17 had 20/20 acuities at their last visit. Visual field sizes ranged from 10º–80º and ERG abnormalities were highly variable as well, with early rod defects followed by cone defects. The earliest sign of disease (found in three children, aged 8–10) was an unusual perivascular cuff of RPE atrophy found surrounding the superior and inferior arcades. This progressed to a diffuse pigmentary retinopathy with choroidal sclerosis. Three patients (ages 40–45) with the disease haplotype were asymptomatic and had completely normal retinal appearances, while their ERG abnormalities were similar to the symptomatic patients.

Conclusions: : We describe a highly variable disease phenotype linked to RP31; with a type I diffuse retinal disease, type III visual field defects and rod–cone degeneration on ERG. Early disease manifestations include unusual perivascular RPE atrophy. Certain affected patients remained asymptomatic at age 40 but exhibited marked ERG abnormalities. Their asymptomatic status correlated with an entirely normal retinal aspect. The ocular phenotype of our family which links to RP31 differs in important ways from the phenotypes associated with the other 12 published ADRP gene defects.

Keywords: electroretinography: clinical • retinal degenerations: hereditary • linkage analysis