Association of codon 108/158 catechol-O-methyltransferase gene polymorphism with the psychiatric manifestations of velo-cardio-facial syndrome
✍ Scribed by Lachman, Herbert M.; Morrow, Bernice; Shprintzen, Robert; Veit, Sabine; Parsia, Sam S.; Faedda, Gianni; Goldberg, Rosalie; Kucherlapati, Raju; Papolos, Demitri F.
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 519 KB
- Volume
- 67
- Category
- Article
- ISSN
- 0148-7299
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✦ Synopsis
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 22qll. 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 22qll. One candidate that has been mapped to this region is catechol-0-methyltransferase (COMT). We recently identified a polymorphism in the COMT gene that leads to a valine-methionine substitution at amino acid 158 of the membrane-bound form of the enzyme. Homozygosity for COMT158met leads to a 3-4fold reduction in enzymatic activity, compared with homozygotes for COMT158'"'. We now report that in a population of patients with VCFS, there is an apparent association between the low-activity allele, COMT15€imet, and the development of bipolar spectrum disorder, and in particular, a rapid-cycling form. 0 1996 Wiley-Liss, Inc.