Novel heterozygous PRPH2 variant identified in a patient with spinocerebellar ataxia type 14 and macular dystrophy

Ophthalmic Genet. 2024 Aug;45(4):409-412. doi: 10.1080/13816810.2024.2321883. Epub 2024 Feb 29.

Abstract

Purpose: To report on a patient with spinocerebellar ataxia type 14 (SCA14) and macular dystrophy with identification of a novel PRPH2 variant.

Methods: Case report.

Results: A 63-year-old female with molecularly confirmed SCA14 presented with symmetric pigmentary disturbances in a perifoveal distribution resembling a pattern macular dystrophy. She had no history of using medications with recognized toxic macular effects. Subsequent genetic testing confirmed a novel heterozygous missense variant of unknown significance in PRPH2 (PRPH2: c.694 G>A, p.(Ala232Thr)).

Conclusions: To our knowledge, this is the first case of macular dystrophy identified in a patient with SCA14. While it is possible that the macular dystrophy observed in this patient might be an under-reported phenotype associated with SCA14, the pattern of macular changes is consistent with PRPH2-related disorders. The identified missense variant is predicted to be damaging by most in silico models, and the residue is highly conserved, adding support to a dual genetic diagnosis in this case.

Keywords: Macular dystrophy; PRKCG; PRPH2; pattern dystrophy; spinocerebellar ataxia type 14.

Publication types

  • Case Reports

MeSH terms

  • Female
  • Heterozygote*
  • Humans
  • Macular Degeneration* / diagnosis
  • Macular Degeneration* / genetics
  • Middle Aged
  • Mutation, Missense*
  • Peripherins* / genetics
  • Phenotype
  • Spinocerebellar Ataxias* / diagnosis
  • Spinocerebellar Ataxias* / genetics

Substances

  • PRPH2 protein, human
  • Peripherins