No abstract

Dominant retinitis pigmentosa phenotype associated with a new mutation in the splicing factor PRPF31Autosomal dominant retinitis pigmentosa results from mutations in 14 known proteins, and at least two further loci have been highlighted by genetic linkage in families (reviewed by the RetNet website; http://www.sph.uth.tmc.edu/Retnet/). The known genes include those encoding components of the phototransduction cascade, retinal transcription factors and retinal structural proteins. 1The list also includes four ubiquitously expressed splicing factors: pre-mRNA processing factor 8 (PRPF8), 2 PRPF31, 3 PRPF3 4 and PAP-1, also known as RP9. 5 6 Splicing is a complex process that involves the precise excision of introns from pre-mRNA by a macromolecular structure called the spliceosome. Three of the splicing factors implicated in autosomal dominant retinitis pigmentosa (ADRP) are components of the U4/U6-U5 tri-snRNP particle, an essential component of the spliceosome.7 8 Mutations in one of these, PRPF31, have been reported to cause between 5 and 20% of ADRP.9 10 In this report, a new mutation in the PRPF31 gene is described, together with the clinical phenotype. CasesThe proband was a 33-year-old female with a corrected visual acuity of 58 and 51 ETDRS letters in the right and left eye, respectively (approximate Snellen equivalents of 6/18 and 6/36). She had a myopic refraction with a spherical equivalence of 22 dioptres in each eye. Nyctalopia had been present since the middle of the second decade, and she had noticed a decrease in her central vision since the beginning of the third decade. At the most recent examination, she had early posterior subscapsular cataract, bone spicule formation in all four quadrants (fig 1a,b) attenuated arterioles and pale optic discs in each eye. The maculae appeared normal on clinical examination. On Goldman perimetry, the mean visual field to the V4e target measured 6.5˚from fixation. Zeiss OCT 3 examination demonstrated a foveal thickness of 170 and 144 microns, respectively, in the right and left eyes, with absence of the third highly reflective band. 11Her younger sister had a similar clinical phenotype and age of onset. The 61-year-old mother was asymptomatic, with unaided visual acuities of 80 and 81 ETDRS letters (Snellen equivalent of 6/7.5). Fundus examination revealed mild bone spicule attenuation in the peripheral retina (fig 1c,d). Visual field to the V4e target on Goldman perimetry was slightly reduced from normal with a mean of 57.8˚from fixation. Foveal thickness on Zeiss OCT 3 examination was 223 and 249 microns in the right and left eyes, respectively. The father of the proband was also asymptomatic with visual acuities of 85 ETDRS letters (Snellen 6/6) in both eyes and normal ocular examinations. No clinical information was available from any other living relative along the maternal line. Mutation screeningDNA from the proband was included in a large cohort of retinal dystrophy DNAs, which were screened for mutations in a limited set of exons or parts of exons of kno...