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

• Published in: Nature genetics Vol. 2; no. 4; pp. 301 - 304
• Main Authors: La Spada, Albert R, Roling, Daniel B, Harding, Anita E, Warner, Carolyn L, Spiegel, Roland, Hausmanowa-Petrusewicz, Irena, Yee, Woon-Chee, Fischbeck, Kenneth H
• Format: Journal Article
• Language: English
• Published: United States 01.12.1992
• Subjects: Base Sequence; DNA - genetics; Female; Genetic Linkage; Genotype; genotypes; Humans; Male; man; meiosis; Meiosis - genetics; Muscular Atrophy, Spinal - genetics; muscular dystrophy; Pedigree; Phenotype; phenotypes; Receptors, Androgen - genetics; Repetitive Sequences, Nucleic Acid; spinal and bulbar muscular atrophy; X Chromosome
• ISSN: 1061-4036; 1546-1718
• 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.