Genotype–Phenotype Study in Autosomal Dominant Retinitis Pigmentosa With PRPF31 Mutations (RP11): Incomplete Penetrance or Variable Expressivity?

Abstract

Purpose: : Autosomal dominant retinitis pigmentosa due to mutation in PRPF31 (RP11) is unusual in that non–penetrance can occur in mutation carriers. The aim was to determine the disease expression in patients from 8 families with defined mutations. The asymptomatic obligate carriers were assessed, in order to determine the prevalence of pre–symptomatic expression of the mutation.

Methods: : 35 patients from 8 families carrying 6 distinct mutations in the PRPF31 gene were ascertained and included 18 affected (20–85 yrs) and 4 asymptomatic obligate carriers (39–77yrs). All underwent ophthalmic examination, color vision testing, digital fundus photography, autofluorescence (AF) imaging and ocular coherence tomography (OCT). Some patients, including obligate carriers, had ISCEV–standard full–field electroretinography (ERG) and Goldman perimetry. Disease variability was assessed between subjects within the same family as well as between different families.

Results: : Age of onset of nightblindness and severity of progression of the disease was variable between members of the same family. Important phenotype variability was noticed among families with different mutations. There was no correlation between phenotype and type of mutation. All asymptomatic obligate carriers had a normal visual acuity and normal fundus appearance. Full–field ERGs revealed generalised rod and cone dysfunction. The AF imaging of one obligate carrier showed a large high density ring bilaterally.

Conclusions: : Mutations in PRPF31 cause a variable phenotype and there is no correlation with the mutation. Those non–penetrant for symptoms and retinal signs may manifest definite abnormalities on electrophysiology and autofluorescence imaging.

Keywords: genetics • gene/expression • electrophysiology: clinical