Retinitis pigmentosa is a clinically and genetically heterogeneous disorder. It is characterized by progressive degeneration of the peripheral retina, leading to night blindness and loss of the peripheral visual field. PRPF31 is one of four pre-mRNA splicing factors identified as causing autosomal dominant retinitis pigmentosa, with incomplete penetrance being the unique feature associated with mutations in this gene. The purpose of this study was to identify PRPF31 mutations in a cohort of 118 cases of autosomal dominant retinitis pigmentosa and determine the genotype-phenotype correlation emerging from the spectrum of mutations in this gene.
Probands with autosomal dominant retinitis pigmentosa underwent ophthalmic evaluation. Blood samples were obtained, genomic DNA was isolated, and PRPF31 exons along with adjacent splice junctions were amplified by PCR and screened by direct sequencing.
In the 118 individuals with autosomal dominant retinitis pigmentosa, six mutations were identified, of which four were novel. One previously known splice site mutation was identified in two other apparently unrelated families.
Mutations in PRPF31 causing adRP were present in nearly 5% of a mixed U.K. population. The age of onset and the severity of the disease varied with different mutations. In addition, individuals carrying the same mutation showed a range of phenotypic variation, suggesting the involvement of other modifying genes.