Abstract
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.
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La Spada, A., Roling, D., Harding, A. et al. Meiotic stability and genotype – phenotype correlation of the trinucleotide repeat in X–linked spinal and bulbar muscular atrophy. Nat Genet 2, 301–304 (1992). https://doi.org/10.1038/ng1292-301
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DOI: https://doi.org/10.1038/ng1292-301
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