Spinocerebellar ataxia type 7 (SCA7) shows a cone-rod dystrophy phenotype.
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 ofSCA7 -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.
Aleman
Tomas S
TS
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cideciyan
Artur V
AV
Volpe
Nicholas J
NJ
Stevanin
Giovanni
G
Brice
Alexis
A
Jacobson
Samuel G
SG
D000328:Adult; D000368:Aged; D000067719:Ataxin-7; D004596:Electroretinography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017949:Retinal Cone Photoreceptor Cells / Q000503:physiopathology; D012162:Retinal Degeneration / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D017948:Retinal Rod Photoreceptor Cells / Q000503:physiopathology; D020754:Spinocerebellar Ataxias / Q000150:complications* / Q000235:genetics / Q000503:physiopathology; D058609:Visual Field Tests; D014794:Visual Fields
C000593829:ATXN7 protein, human; D000067719:Ataxin-7; D009419:Nerve Tissue Proteins