Clinical characterization of retinitis pigmentosa associated with variants in SNRNP200

Importance  SNRNP200 is a recently identified genetic cause of autosomal dominant retinitis pigmentosa (RP). However, the associated retinal phenotype is not well characterized. Objective  To describe the retinal phenotype in patients with RP secondary to variants in SNRNP200. Design, Setting, and Participants  This retrospective, case-series study was performed at 2 tertiary referral centers for inherited retinal diseases. Participants included 9 consecutive patients from 8 families with RP attributed to variants in SNRNP200. Data were collected from August 2017 to March 2018 and analyzed from May to July 2018. Main Outcomes and Measures  Results of clinical evaluation, multimodal retinal imaging, and molecular genetic testing using targeted next-generation sequencing. Results  Of the 9 patients included in the analysis (4 female and 5 male; mean [SD] age at presentation, 19 [15] years), each presented with nyctalopia, typically in the first 2 decades of life, although 2 patients experienced symptom onset in middle age. None had any consistent systemic features suggestive of syndromic RP. Retinal imaging studies and electroretinography findings were typical of a rod-predominant dystrophy with later involvement of cone photoreceptors. Phenotypic heterogeneity was typified by 4 unrelated patients with the common c.2041C>T SNRNP200 variant who demonstrated a variable age of disease onset (middle teenage years to the fourth decade of life). Disease progression was slow, with all but 1 patient maintaining visual acuity of better than 20/40 in the better-seeing eye in the fifth and sixth decades of life. Conclusions and Relevance  These data suggest that variants in SNRNP200 result in nonsyndromic RP with a typical phenotype of a rod-predominant dystrophy. Significant phenotypic heterogeneity and nonpenetrance were noted within some affected families. Symptom onset was typically within the first 2 decades of life, with slow progression and well-preserved visual acuities into the fifth and sixth decades.