Meiotic stability and genotype-phenotype correlation of the trinucleotide repeat in X-linked spinal and bulbar muscular atrophy.
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.
La Spada
A R
AR
Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia 19104-6146.
Roling
D B
DB
Harding
A E
AE
Warner
C L
CL
Spiegel
R
R
Hausmanowa-Petrusewicz
I
I
Yee
W C
WC
Fischbeck
K H
KH
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
D011944:Receptors, Androgen; D004247:DNA