TY - JOUR
T1 - Clinical characterization of patients with PRPF31-related retinitis pigmentosa and asymptomatic carriers
T2 - a cross-sectional study
AU - Lisbjerg, Kristian
AU - Bertelsen, Mette
AU - Grønskov, Karen
AU - Kessel, Line
PY - 2023/10
Y1 - 2023/10
N2 - BACKGROUND/AIM: To describe the clinical phenotype of retinitis pigmentosa (RP) caused by PRPF31-variants and clinical characterization of asymptomatic PRPF31 carriers.MATERIALS AND METHODS: We conducted a descriptive cross-sectional deep phenotyping study. We included subjects with PRPF31 variants predicted to be disease-causing, both individuals with RP and asymptomatic carriers. Participants underwent a comprehensive clinical examination of standard visual function parameters (visual acuity, contrast sensitivity, Goldmann visual field), full-field stimulus threshold (FST), full-field electroretinogram (ff-ERG), and a structural investigation with slit lamp and multimodal imaging. We used Spearman correlation analyses to evaluate associations between quantitative outcomes.RESULTS: We included 21 individuals with disease-causing PRPF31-variants: 16 symptomatic and 5 asymptomatic subjects. The symptomatic subjects demonstrated a typical RP phenotype with constricted visual fields, extinguished ff-ERG, and disrupted outer retinal anatomy. FST was impaired and correlated significantly with other outcome measures in RP subjects. Structure-function correlations with Spearman correlation analysis showed moderate correlation coefficients due to a few outliers in each analysis. The asymptomatic individuals had normal best-corrected visual acuity and visual fields, but showed reduced ff-ERG amplitudes, borderline FST sensitivity, and structural abnormalities on OCT and fundoscopy.CONCLUSIONS: RP11 has a typical RP phenotype but varies in terms of severity. FST measurements correlated well with other functional and structural metrics and may be a reliable outcome measure in future trials as it is sensitive to a broad range of disease severities. Asymptomatic carriers showed sub-clinical disease manifestations, and our findings underline that reported non-penetrance in PRPF31-related RP is not an all-or-none phenomenon.
AB - BACKGROUND/AIM: To describe the clinical phenotype of retinitis pigmentosa (RP) caused by PRPF31-variants and clinical characterization of asymptomatic PRPF31 carriers.MATERIALS AND METHODS: We conducted a descriptive cross-sectional deep phenotyping study. We included subjects with PRPF31 variants predicted to be disease-causing, both individuals with RP and asymptomatic carriers. Participants underwent a comprehensive clinical examination of standard visual function parameters (visual acuity, contrast sensitivity, Goldmann visual field), full-field stimulus threshold (FST), full-field electroretinogram (ff-ERG), and a structural investigation with slit lamp and multimodal imaging. We used Spearman correlation analyses to evaluate associations between quantitative outcomes.RESULTS: We included 21 individuals with disease-causing PRPF31-variants: 16 symptomatic and 5 asymptomatic subjects. The symptomatic subjects demonstrated a typical RP phenotype with constricted visual fields, extinguished ff-ERG, and disrupted outer retinal anatomy. FST was impaired and correlated significantly with other outcome measures in RP subjects. Structure-function correlations with Spearman correlation analysis showed moderate correlation coefficients due to a few outliers in each analysis. The asymptomatic individuals had normal best-corrected visual acuity and visual fields, but showed reduced ff-ERG amplitudes, borderline FST sensitivity, and structural abnormalities on OCT and fundoscopy.CONCLUSIONS: RP11 has a typical RP phenotype but varies in terms of severity. FST measurements correlated well with other functional and structural metrics and may be a reliable outcome measure in future trials as it is sensitive to a broad range of disease severities. Asymptomatic carriers showed sub-clinical disease manifestations, and our findings underline that reported non-penetrance in PRPF31-related RP is not an all-or-none phenomenon.
KW - Cross-Sectional Studies
KW - Electroretinography
KW - Eye Proteins/genetics
KW - Heterozygote
KW - Humans
KW - Retina
KW - Retinitis Pigmentosa/diagnosis
KW - Retinitis pigmentosa
KW - FST
KW - asymptomatic carriers
KW - RP11
KW - PRPF31
KW - non-penetrance
UR - http://www.scopus.com/inward/record.url?scp=85161691713&partnerID=8YFLogxK
U2 - 10.1080/13816810.2023.2219732
DO - 10.1080/13816810.2023.2219732
M3 - Journal article
C2 - 37293790
SN - 1381-6810
VL - 44
SP - 456
EP - 464
JO - Ophthalmic Genetics
JF - Ophthalmic Genetics
IS - 5
ER -