Clinical Characterization of Retinitis Pigmentosa Associated With Variants in SNRNP200

TY - JOUR

T1 - Clinical Characterization of Retinitis Pigmentosa Associated With Variants in SNRNP200

AU - Yusuf, Imran H

AU - Birtel, Johannes

AU - Shanks, Morag E

AU - Clouston, Penny

AU - Downes, Susan M

AU - Charbel Issa, Peter

AU - MacLaren, Robert E

PY - 2019/11/1

Y1 - 2019/11/1

N2 - 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.

AB - 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.

U2 - 10.1001/jamaophthalmol.2019.3298

DO - 10.1001/jamaophthalmol.2019.3298

M3 - SCORING: Journal article

C2 - 31486839

VL - 137

SP - 1295

EP - 1300

JO - JAMA OPHTHALMOL

JF - JAMA OPHTHALMOL

SN - 2168-6165

IS - 11

ER -