Abstract
Individuals with primary trimethylaminuria exhibit a body odour reminiscent of rotting fish, due to excessive excretion of trimethylamine (TMA; refs 1–3). The disorder, colloquially known as fish-odour syndrome, is inherited recessively as a defect in hepatic N-oxidation of dietary-derived TMA4–6 and cannot be considered benign, as sufferers may display a variety of psychosocial reactions, ranging from social isolation to clinical depression and attempted suicide6. TMA oxidation is catalyzed by flavin-containing mono-oxygenase (FMO; refs 7,8), and tissue localization9,10 and functional studies11 have established FMO3 as the form most likely to be defective in fish-odour syndrome. Direct sequencing of the coding exons of FMO3 amplified from a patient with fish-odour syndrome identified two missense mutations. Although one of these represented a common polymorphism, the other, a C→T transition in exon 4, was found only in an affected pedigree, in which it segregated with the disorder. The latter mutation predicts a proline→leucine substitution at residue 153 and abolishes FMO3 catalytic activity. Our results indicate that defects in FMO3 underlie fish-odour syndrome and that the Pro153→Leu153 mutation described here is a cause of this distressing condition.
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Dolphin, C., Janmohamed, A., Smith, R. et al. Missense mutation in flavin-containing mono-oxygenase 3 gene, FMO3, underlies fish-odour syndrome. Nat Genet 17, 491–494 (1997). https://doi.org/10.1038/ng1297-491
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DOI: https://doi.org/10.1038/ng1297-491
