TY - JOUR
T1 - Association of Codon 108/158 Catechol-O-Methyltransferase Gene Polymorphism with the Psychiatric Manifestations of Velo-Cardio-Facial Syndrome
AU - Lachman, Herbert M.
AU - Morrow, Bernice
AU - Shprintzen, Robert
AU - Veit, Sabine
AU - Parsia, Sam S.
AU - Faedda, Gianni
AU - Goldberg, Rosalie
AU - Kucherlapati, Raju
AU - Papolos, Demitri F.
PY - 1996/9/20
Y1 - 1996/9/20
N2 - Velo-cardio-facial-syndrome (VCFS) is a common congenital disorder associated with typical facial appearance, cleft palate, cardiac defects, and learning disabilities. The majority of patients have an interstitial deletion on chromosome 22q11. In addition to physical abnormalities, a variety of psychiatric illnesses have been reported in patients with VCFS, including schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder. The psychiatric manifestations of VCFS could be due to haploin-sufficiency of a gene(s) within 22q11. One candidate that has been mapped to this region is catechol-O-methyltransferase (COMT). We recently identified a polymorphism in the COMT gene that leads to a valine→methionine substitution at amino acid 58 of the membrane-bound form of the enzyme. Homozygosity for COMT158met leads to a 3-4-fold reduction in enzymatic activity, compared with homozygotes for COMT158val. We now report that in a population of patients with VCFS, there is an apparent association between the low-activity allele, COMT158met, and the development of bipolar spectrum disorder, and in particular, a rapid-cycling form.
AB - Velo-cardio-facial-syndrome (VCFS) is a common congenital disorder associated with typical facial appearance, cleft palate, cardiac defects, and learning disabilities. The majority of patients have an interstitial deletion on chromosome 22q11. In addition to physical abnormalities, a variety of psychiatric illnesses have been reported in patients with VCFS, including schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder. The psychiatric manifestations of VCFS could be due to haploin-sufficiency of a gene(s) within 22q11. One candidate that has been mapped to this region is catechol-O-methyltransferase (COMT). We recently identified a polymorphism in the COMT gene that leads to a valine→methionine substitution at amino acid 58 of the membrane-bound form of the enzyme. Homozygosity for COMT158met leads to a 3-4-fold reduction in enzymatic activity, compared with homozygotes for COMT158val. We now report that in a population of patients with VCFS, there is an apparent association between the low-activity allele, COMT158met, and the development of bipolar spectrum disorder, and in particular, a rapid-cycling form.
KW - Bipolar disorder
KW - Catecholamine O-methyltransferase
KW - Rapid cycling
KW - Schizophrenia
KW - Velocardio-facial syndrome
UR - http://www.scopus.com/inward/record.url?scp=0029745410&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029745410&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1096-8628(19960920)67:5<468::AID-AJMG5>3.0.CO;2-G
DO - 10.1002/(SICI)1096-8628(19960920)67:5<468::AID-AJMG5>3.0.CO;2-G
M3 - Article
C2 - 8886163
AN - SCOPUS:0029745410
SN - 0148-7299
VL - 67
SP - 468
EP - 472
JO - American Journal of Medical Genetics - Seminars in Medical Genetics
JF - American Journal of Medical Genetics - Seminars in Medical Genetics
IS - 5
ER -