Human Molecular Genetics, Vol 7, 839-845, Copyright © 1998 by Oxford University Press
EP Treacy, BR Akerman, LML Chow, R Youil, C Bibeau, J Lin, AG Bruce, M Knight, DM Danks, JR Cashman and SM Forrest
Individuals with the recessive condition trimethylaminuria exhibit
variation in metabolic detoxication of xenobiotics by hepatic flavin-
containing monooxygenases. We show here that mutations in the human
flavin-containing monooxygenase isoform 3 gene ( FMO3 ) impair N -
oxygenation of xenobiotics and are responsible for the trimethylaminuria
phenotype. Three disease-causing mutations in nine Australian-born probands
have been identified which share a particular polymorphic haplotype.
Nonsense and missense mutations are associated with a severe phenotype and
are also implicated in impaired metabolism of other nitrogen- and
sulfur-containing substrates including biogenic amines, both clinically and
when mutated proteins expressed from cDNA are studied in vitro . These
findings illustrate the critical role played by human FMO3 in the
metabolism of xenobiotic substrates and endogenous amines.
ARTICLES
Mutations of the flavin-containing monooxygenase gene (FMO3) cause trimethylaminuria, a defect in detoxication
McGill University, Montreal Children's Hospital Research Institute, Montreal, Quebec H3H 1P3, Canada. mcet@musica.mcgill.ca
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