Phenotypic variability in PRPH2 as demonstrated by a family with incomplete penetrance of autosomal dominant cone-rod dystrophy

Doc Ophthalmol. 2023 Jun;146(3):267-272. doi: 10.1007/s10633-022-09916-5. Epub 2023 Jan 7.

Abstract

Introduction: Mutations in the peripherin-2 gene (PRPH2) are a common cause of inherited retinal dystrophies well known for their phenotypic diversity. We describe a novel presentation of the c.623G > A; p.(Gly208Asp) variant in association with cone-rod dystrophy and reduced penetrance.

Case description: A 39-year-old man presents with a history of decreased visual acuity, photophobia, and dyschromatopsia. Fundus examination was largely unremarkable while spectral-domain optical coherence tomography (SD-OCT) demonstrated diffuse granularity at the ellipsoid zone. Full-field electroretinogram (ffERG) revealed a cone-rod dystrophy. Genetic testing revealed a heterozygous pathogenic variant, c.623G > A; p.(Gly208Asp), in the PRPH2 gene, also found in an unaffected brother. The 50-year-old brother had no visual symptoms and no findings on fundus examination. SD-OCT showed normal retinal architecture and ffERG was within normal limits bilaterally.

Conclusion: This case report broadens the known phenotypic presentations of PRPH2-associated retinopathy and suggests that the PRPH2 variant c.623G > A; p.(Gly208Asp) may be associated with reduced penetrance.

Keywords: Cone-rod dystrophy; Incomplete penetrance; Inherited retinal dystrophy; PRPH2.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Biological Variation, Population
  • Cone-Rod Dystrophies* / diagnosis
  • Cone-Rod Dystrophies* / genetics
  • Electroretinography
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Penetrance
  • Phenotype
  • Retinitis Pigmentosa* / diagnosis
  • Retinitis Pigmentosa* / genetics
  • Tomography, Optical Coherence