Homozygosity enhances severity in spinocerebellar ataxia type 3

Pediatr Neurol. 2008 Apr;38(4):296-9. doi: 10.1016/j.pediatrneurol.2007.12.006.

Abstract

Spinocerebellar ataxia type 3, or Machado-Joseph disease, is an autosomal dominant neurodegenerative disease characterized by a wide spectrum of clinical findings that include progressive cerebellar ataxia. All affected individuals have an expanded CAG repeat mutation in one allele of the ATXN3 gene. An inverse relationship exists between the age of onset and the number of repeats in the abnormal expanded allele. The case described is that of a child with Machado-Joseph disease, daughter of a consanguineous affected couple. She inherited the expanded allele in homozygosity with CAG repeat size similar to that of her parents, and had a distinct early onset (4 years of age) and severe clinical phenotype. This case supports the conclusion that homozygosity aggravates the clinical phenotype. Loss of function of the normal expressed ataxin-3, or possibly aggregation of ataxin-3, may be implicated in disease mechanism.

Publication types

  • Case Reports

MeSH terms

  • Ataxin-3
  • Child, Preschool
  • Female
  • Homozygote*
  • Humans
  • Machado-Joseph Disease / genetics*
  • Machado-Joseph Disease / pathology*
  • Nerve Tissue Proteins / genetics*
  • Nuclear Proteins / genetics*
  • Pedigree
  • Phenotype
  • Repressor Proteins / genetics*
  • Severity of Illness Index

Substances

  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Repressor Proteins
  • ATXN3 protein, human
  • Ataxin-3