Meiotic stability and genotype-phenotype correlation of the trinucleotide repeat in X-linked spinal and bulbar muscular atrophy

Nat Genet. 1992 Dec;2(4):301-4. doi: 10.1038/ng1292-301.


Expansion of the trinucleotide repeat (CAG)n in the first exon of the androgen receptor gene is associated with a rare motor neuron disorder, X-linked spinal and bulbar muscular atrophy. We have found that expanded (CAG)n alleles undergo alteration in length when transmitted from parent to offspring. Of 45 meioses examined, 12 (27%) demonstrated a change in CAG repeat number. Both expansions and contractions were observed, although their magnitude was small. There was a greater rate of instability in male meiosis than in female meiosis. We also found evidence for a correlation between disease severity and CAG repeat length, but other factors seem to contribute to the phenotypic variability in this disorder.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • DNA / genetics
  • Female
  • Genetic Linkage
  • Genotype
  • Humans
  • Male
  • Meiosis / genetics
  • Muscular Atrophy, Spinal / genetics*
  • Pedigree
  • Phenotype
  • Receptors, Androgen / genetics
  • Repetitive Sequences, Nucleic Acid*
  • X Chromosome*


  • Receptors, Androgen
  • DNA