Clinical and Genetic Findings in a Cohort of Patients with PRPF31-Associated Retinal Dystrophy

Am J Ophthalmol. 2024 Nov:267:213-229. doi: 10.1016/j.ajo.2024.06.020. Epub 2024 Jun 22.

Abstract

Purpose: The purpose of our study was to assess the phenotypic and genotypic spectrum in a large cohort of patients with PRPF31-associated retinal dystrophy.

Design: Retrospective cohort study.

Methods: In this retrospective chart review study, we collected cross-sectional data on the phenotype and genotype of patients with PRPF31-associated retinal dystrophy from the clinics for inherited retinal dystrophies at the University of Tuebingen and the local RetDis database and biobank. Patients underwent thorough ophthalmological examinations and genetic testing.

Results: Eighty-six patients from 61 families were available for clinical assessment, while genomic DNA was available for 111 individuals (index patients and family members). Fifty-three different disease-associated variants were observed in our cohort. Point mutations were the most common class. All but two patients exhibited features of a typical Retinitis pigmentosa (RP). One patient showed a cone-rod dystrophy pattern. One mutation carrier revealed no signs of a retinal dystrophy. There was a statistically significant better visual acuity for patients with large deletions in the 20-39 age group. Cystoid macular edema was common in those with preserved central retina and showed an association with female sex.

Conclusion: Our study confirms high phenotypic variability in disease onset and age at which legal blindness is reached in PRPF31-associated RP. Non-penetrance is commonly documented in family history, although poorly represented in our study, possibly indicating that true asymptomatic mutation carriers are rare if followed-up over lifetime with thorough ophthalmologic workup.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Cross-Sectional Studies
  • DNA Mutational Analysis
  • Electroretinography
  • Eye Proteins* / genetics
  • Female
  • Genetic Testing
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Pedigree
  • Phenotype*
  • Retinal Dystrophies / diagnosis
  • Retinal Dystrophies / genetics
  • Retinal Dystrophies / physiopathology
  • Retinitis Pigmentosa / diagnosis
  • Retinitis Pigmentosa / genetics
  • Retinitis Pigmentosa / physiopathology
  • Retrospective Studies
  • Tomography, Optical Coherence
  • Visual Acuity* / physiology
  • Young Adult

Substances

  • Eye Proteins
  • PRPF31 protein, human