Detection of the Machado-Joseph disease/spinocerebellar ataxia three trinucleotide repeat expansion in families with autosomal dominant motor disorders, including the Drew family of Walworth

Brain. 1995 Oct:118 ( Pt 5):1077-85. doi: 10.1093/brain/118.5.1077.

Abstract

Affected members of 63 families with a variety of autosomal dominant late onset cerebellar ataxias (ADCA), and 29 patients with similar phenotypes but no affected relatives, were investigated for the trinucleotide (CAG) repeat expansion described in Japanese families with Machado-Joseph disease (MJD). This disorder had previously been shown to map to the region of chromosome 14 which also contains a locus causing ADCA in French families, spinocerebellar ataxia 3 (SCA3). The MJD/SCA3 mutation was identified in nine families with ADCA type I, and a further family in which affected members had parkinsonism, peripheral neuropathy, dystonia, and spasticity, but little evidence of cerebellar disease. Only one of the 10 families was British (the Drew family of Walworth); the others originated from India, Jamaica, Ghana, Brazil and France. There was no single clinical feature which distinguished patients with the MJD/SCA3 mutation from those with the CAG expansion on chromosome 6 (SCA1) or ADCA type I families with no known mutation. The CAG repeat length ranged from 13-41 copies on normal chromosomes and 62-80 copies on affected chromosomes. There was a significant inverse correlation between age of onset of symptoms and repeat length, but no significant effect of parental sex on repeat length or age of onset in offspring. DNA analysis for the MJD/SCA3 mutation is useful for diagnosis in patients with familial ataxic or extrapyramidal syndromes, and will aid genetic counselling in these disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • DNA / analysis
  • DNA / blood
  • Female
  • Humans
  • Machado-Joseph Disease / diagnosis
  • Machado-Joseph Disease / genetics*
  • Male
  • Middle Aged
  • Mutation / genetics
  • Pedigree
  • Phenotype
  • Repetitive Sequences, Nucleic Acid*
  • Spinocerebellar Degenerations / diagnosis*
  • Spinocerebellar Degenerations / genetics*

Substances

  • DNA