Association of codon 108/158 catechol-O-methyltransferase gene polymorphism with the psychiatric manifestations of velo-cardio-facial syndrome

Journal Article · Fri Sep 20 00:00:00 EDT 1996 · American Journal of Medical Genetics

DOI:https://doi.org/10.1002/(SICI)1096-8628(19960920)67:5<468::AID-AJMG5>3.0.CO;2-G· OSTI ID:539227

Lachman, H M; Papolos, D F; Veit, S ^[1]

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1. Albert Einstein College of Medicine, Bronx, NY (United States); and others

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 haploinsufficiency 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{r_arrow}methionine substitution at amino acid 158 of the membrane-bound form of the enzyme. Homozygosity for COMT158{sup met} leads to a 3- to 4-fold reduction in enzymatic activity, compared with homozygotes for COMT158{sup met}. We now report that in a population of patients with VCFS, there is an apparent association between the low-activity allele, COMT158{sup met}, and the development of bipolar spectrum disorder, and in particular, a rapid-cycling form. 33 refs., 3 tabs.

• OSTI ID: 539227
• Journal Information: American Journal of Medical Genetics, Vol. 67, Issue 5; Other Information: PBD: 20 Sep 1996
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
PATIENTS
HEREDITARY DISEASES
MENTAL DISORDERS
CONGENITAL DISEASES
CONGENITAL MALFORMATIONS
PHENOTYPE
PYROCATECHOL
GENE MUTATIONS
GENETIC MAPPING
MUTATION FREQUENCY
DNA SEQUENCING
ENZYME ACTIVITY
HUMAN CHROMOSOME 22
CHROMOSOMAL ABERRATIONS
CODONS
AMINO ACID SEQUENCE
IN-SITU HYBRIDIZATION
FLUORESCENCE