Skip to content

Biallelic RP1 study has expanded the mutational and clinical spectrum of retinitis pigmentosa. 

A research study on genetic diagnosis testing for biallelic RP1 has found a broad spectrum of retinal disease identifying the largest reported group of unrelated patients with recessive associated disease.  Researchers from the Massachusetts Eye and Ear, Harvard Medical School, Boston, and Casey Eye Institute, Oregon Health & Science University, Portland, have shown that a significant contributor to disease can be associated with a considerably later onset of RP (retinitis pigmentosa) rather than that typically associated with biallelic RP1 mutations.  The research is understood to extend a more comprehensive natural history for RP1-associated dystrophies and potentially undercover valuable therapeutic strategies.


RP are caused by over three thousand mutations in more than 80 genes, one of which, RP1, encodes the photoreceptor-specific microtubule-associated protein residing in the outer segment of rods and cones.  RP1 functions for the stability and organization of the outer segment discs however, RP1-autosomal dominant RP (adRP) manifests nyctalopia and decreased peripheral vision in their 20s and 30s with near-normal visual acuity (VA) into their 50s and 60s.  In contrast, this research has identified that the autosomal recessive RP (arRP) inheritance pattern typically manifests before 10 years of age, and is characterized by secondary macular involvement that can result in legal blindness by age 20 years. RP1 is now estimated to cause up to 11% of each adRP and arRP.  The current research is now focused on evaluating the phenotypic spectrum and genotypic associations of autosomal recessive RP1.


Results of the study were reported from nineteen eligible patients from 17 families ranging from 10 to 56 years of age. Autosomal recessive inheritance of nineteen patients comprised diverse ethnicity with countries of origin including Brazil, Kuwait, Saudi Arabia, Malaysia, Vietnam, and the United States.  Ten of the 21 unique RP1 variants identified were novel, and mutations within exon 2 accounted for nearly half of alleles across the cohort, including clinical diagnoses of retinitis pigmentosa (13), cone-rod dystrophy (3), Leber congenital amaurosis (1), early-onset severe retinal dystrophy (1), and macular dystrophy (1). Patients with later-onset disease, including retinitis pigmentosa, had at least one missense variant in an exon 2 DCX (doublecortin) domain.  Commenting on the study, researchers stated that “this cohort of patients broadens the phenotypic spectrum of biallelic RP1-associated retinal dystrophies to include later-onset RP, and it demonstrates the clinical significance of missense mutations in the exon 2 DCX 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.”