Prevalence of Huntington's disease gene CAG trinucleotide repeat alleles in patients with bipolar disorder.
OBJECTIVE
Huntington's disease is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms that are caused by huntingtin gene (HTT) CAG trinucleotide repeat alleles of 36 or more units. A greater than expected prevalence of incompletely penetrant HTT CAG repeat alleles observed among individuals diagnosed with major depressive disorder raises the possibility that another mood disorder, bipolar disorder, could likewise be associated with Huntington's disease.


METHODS
We assessed the distribution of HTT CAG repeat alleles in a cohort of individuals with bipolar disorder. HTT CAG allele sizes from 2,229 Caucasian individuals diagnosed with DSM-IV bipolar disorder were compared to allele sizes in 1,828 control individuals from multiple cohorts.


RESULTS
We found that HTT CAG repeat alleles > 35 units were observed in only one of 4,458 chromosomes from individuals with bipolar disorder, compared to three of 3,656 chromosomes from control subjects.


CONCLUSIONS
These findings do not support an association between bipolar disorder and Huntington's disease.
Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.|UnIGENe, IBMC - Institute for Molecular and Cell Biology, University of Porto, Porto, Portugal.
Eliana Marisa
EM
Ramos
Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
Tammy
T
Gillis
Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
Jayalakshmi S
JS
Mysore
Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
Jong-Min
JM
Lee
UnIGENe, IBMC - Institute for Molecular and Cell Biology, University of Porto, Porto, Portugal.
Isabel
http://orcid.org/0000-0001-8549-6903
I
Alonso
Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
James F
JF
Gusella
Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
Jordan W
JW
Smoller
Division of Psychiatric Genomics, Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA.
Pamela
P
Sklar
Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
Marcy E
ME
MacDonald
Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
Roy H
RH
Perlis
D000328:Adult; D000483:Alleles; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics; D001714:Bipolar Disorder / Q000235:genetics; D003865:Major Depressive Disorder / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019683:Penetrance; D015995:Prevalence; D013223:Statistics as Topic; D018911:Trinucleotide Repeats / Q000235:genetics*
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins
Huntington's disease; bipolar disorder; depression; neurodegenerative disease; polyglutamine expansion; trinucleotide repeat