title: Meiotic stability and genotype-phenotype correlation of the trinucleotide repeat in X-linked spinal and bulbar muscular atrophy.
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.
authors.affiliation: Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia 19104-6146.
authors.forename: A R
authors.initials: AR
authors.lastname: La Spada
authors.forename: D B
authors.initials: DB
authors.lastname: Roling
authors.forename: A E
authors.initials: AE
authors.lastname: Harding
authors.forename: C L
authors.initials: CL
authors.lastname: Warner
authors.forename: R
authors.initials: R
authors.lastname: Spiegel
authors.forename: I
authors.initials: I
authors.lastname: Hausmanowa-Petrusewicz
authors.forename: W C
authors.initials: WC
authors.lastname: Yee
authors.forename: K H
authors.initials: KH
authors.lastname: Fischbeck
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D008297:Male; D008540:Meiosis / Q000235:genetics; D009134:Muscular Atrophy, Spinal / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011944:Receptors, Androgen / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D014960:X Chromosome
chemical_list: D011944:Receptors, Androgen; D004247:DNA