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The hypothesis that expanded trinucleotide repeats (TNRs) contribute to the pathogenesis
of bipolar disorder has received strong support from recent studies showing that,
on average, bipolar patients carry larger repeat sequences of the TNR motif CAG/CTG
than do controls. It has been postulated that intergenerational expansion of a TNR
may be responsible for the tendency for age of onset to become earlier in younger
generations (anticipation) observed in some bipolar pedigrees, and that length polymorphism
may account for variability in clinical phenotype. We have used the method of repeat
expansion detection to examine these predictions in a sample of 133 Caucasian DSM-III-R
bipolar I probands from the British Isles. We found no evidence to support the notion
that CAG/CTG TNR genes are major determinants of phenotypic severity or age at onset
in the population examined, and conclude that for most cases of bipolar disorder TNR
genes may operate as susceptibility genes rather than as single genes of major effect.
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Article info
Publication history
Received in revised form:
November 13,
1996
Received:
April 15,
1996
Identification
Copyright
© 1997 Society of Biological Psychiatry. Published by Elsevier Inc.
