Spinocerebellar ataxia type 7 (SCA7) shows a cone-rod dystrophy phenotype

Tomas S. Aleman, Artur V. Cideciyan, Nicholas J. Volpe, Giovanni Stevanin, Alexis Brice, Samuel G. Jacobson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

Autosomal dominant spinocerebellar ataxia 7 is associated with retinal degeneration. SCA7, the causative gene, encodes ataxin-7, a ubiquitous 892 amino acid protein of variable sub-cellular localization, and the disease is due to expansion of an unstable CAG repeat in the coding region of the gene. Recent increases in understanding of the mechanisms of SCA7-related retinopathy from in vitro and murine model studies prompted us to perform a detailed study of the retinal phenotype of affected members of a family with SCA7 mutation (45-47 CAG repeats). There was a spectrum of severity from mild to severe dysfunction. Early functional abnormalities were at both photoreceptor and post-receptoral levels. When cone and rod photoreceptor dysfunction was present, it was approximately equal. Regional retinal dysfunction was evident: there was more dysfunction centrally than peripherally with least effect in the midperiphery. In vivo cross-sectional retinal images with optical coherence tomography showed an early disease stage of altered foveal lamination (abnormal area of low reflectivity splitting the outer retina-choroidal complex) accompanied in the parafovea by reduced retinal thickness. Later disease stages showed foveal and parafoveal retinal thinning. The phenotype in this family with SCA7 is that of a cone-rod dystrophy. These observations increase interest in a recent hypothesis that ataxin-7 may interfere with the function of CRX (cone-rod homeobox), a transcription factor regulating photoreceptor genes and a cause of a cone-rod dystrophy phenotype in man.

Original languageEnglish (US)
Pages (from-to)737-745
Number of pages9
JournalExperimental eye research
Volume74
Issue number6
DOIs
StatePublished - 2002

Keywords

  • Ataxin
  • Cone
  • Polyglutamine disease
  • Repeat expansions
  • Retinal degeneration
  • Rod
  • Spinocerebellar ataxia

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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