Association of Codon 108/158 Catechol-O-Methyltransferase Gene Polymorphism with the Psychiatric Manifestations of Velo-Cardio-Facial Syndrome

Herbert M. Lachman, Bernice Morrow, Robert Shprintzen, Sabine Veit, Sam S. Parsia, Gianni Faedda, Rosalie Goldberg, Raju Kucherlapati, Demitri F. Papolos

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260 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)468-472
Number of pages5
JournalAmerican Journal of Medical Genetics - Seminars in Medical Genetics
Issue number5
StatePublished - Sep 20 1996



  • Bipolar disorder
  • Catecholamine O-methyltransferase
  • Rapid cycling
  • Schizophrenia
  • Velocardio-facial syndrome

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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