A research group, based at the Massachusetts Eye and Ear, Harvard Medical School, Boston, and Oregon Health & Science University, Portland, has published a new study on RP1 mutations identifying a broad spectrum of retinal disease. The research outlined an expanding phenotypic spectrum of biallelic RP1-associated retinal dystrophies. The researchers assessed a larger cohort of patients in the study, the results of which may be valuable for considering novel therapeutic strategies, including patient-derived iPSCs technologies or gene therapy.
RP1 encodes a photoreceptor-specific microtubule-associated protein that is located in the outer segments of both rods and cones, and whose primary function is the stability and organization of outer segment discs. In previous research, mutations in RP1 were initially identified as autosomal dominant RP (adRP), and subsequently identified with autosomal recessive RP (arRP). According to the researchers, the onset and severity of RP1-associated RP are related to the mode of inheritance and clinically includes characteristics of nyctalopia and decreased peripheral vision in patients into their 20s and 30s and then near-normal visual acuity (VA) among patients into their 50s and 60s. In recessive mutations in RP1, typically the disorder manifests before 10 years of age and is characterized by secondary macular involvement, followed by legal blindness by age 20 years of age.
In the current study, nineteen eligible patients were identified and ranged in age from 10 to 56 years, reporting that, “ten of the 21 unique RP1 variants identified were novel, and mutations within exon 2 accounted for nearly half of alleles across the cohort”. Thirteen clinical diagnoses had retinitis pigmentosa, 3 patients had cone-rod dystrophy, and one patient each had Leber congenital amaurosis, early-onset severe retinal dystrophy and macular dystrophy. In addition, symptom onset occurred between 4 and 30 years of age and there were clusters of onset age that correlated with the effects of RP1 mutations at a protein level. In commenting in the study, researchers stated that “data from this cohort, which to our knowledge represents the largest reported group of unrelated patients with biallelic RP1-associated disease, further broaden the phenotypic spectrum of biallelic disease and demonstrate the clinical importance of the DCX homology domains. A prospective natural history study of RP1-associated dystrophies would be of value in assessing and understanding this clinical heterogeneity in a larger group of patients’.