Expanded trinucleotide CAG repeats in families with bipolar affective disorder.
Clinical anticipation has been reported in bipolar affective disorder (BPAD). The hypothesis that expanded trinucleotide repeats are related to anticipation and transmission pattern in families with bipolar affective disorder is tested in this study. Eighty-seven two-generation pairs of patients recruited from 29 bipolar families were analyzed. The repeat expansion detection method was used to detect CAG repeat expansions between successive generations. Significant changes in age at onset and episode frequency in successive generations were observed. Mean trinucleotide CAG repeat length between parental and offspring generation significantly increased when the phenotype increased in severity, i.e., changed from major depression, single episode or unipolar recurrent depression to BPAD. A parent-of-origin effect was also observed with a significant increase in median length CAG between G1 and G2 with maternal inheritance. This increase was observed notably in female offspring. Our findings indicate for the first time that expansion of CAG repeat length could explain the clinical observation of anticipation in families with BPAD. These results provide further support for expanded trinucleotide repeat sequences as risk factors in major affective disorders.
Mendlewicz
J
J
Department of Psychiatry, University Clinics of Brussels, Erasme Hospital, Free University of Brussels, Belgium.
Lindbald
K
K
Souery
D
D
Mahieu
B
B
Nylander
P O
PO
De Bruyn
A
A
Zander
C
C
Engström
C
C
Adolfsson
R
R
Van Broeckhoven
C
C
Schalling
M
M
Lipp
O
O
D000328:Adult; D017668:Age of Onset; D001714:Bipolar Disorder / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D004247:DNA / Q000032:analysis / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D010641:Phenotype; D018911:Trinucleotide Repeats / Q000235:genetics*
D004247:DNA