title: Trimethylaminuria (fish odor syndrome): genotype characterization among Portuguese patients.
abstract: Trimethylaminuria (TMAu) or "fish odor syndrome" is a metabolic disorder characterized by the inability to convert malodorous dietarily-derived trimethylamine (TMA) to odorless TMA N-oxide by the flavin-containing monooxygenase 3 (FMO3). Affected individuals unable to complete this reaction exude a "fishy" body odor due to the secretion of TMA in their corporal fluids leading to a variety of psychosocial problems. Interindividual variability in the expression of FMO3 gene may affect drug and foreign chemical metabolism in the liver and other tissues. Therefore, it is important to screen for common TMAu mutations but also extend the search to other genetic variants in order to correlate genotype and disease-associated phenotypes. In this study, 25 Portuguese patients with phenotype suggestive of TMAu were evaluated for molecular screening of the FMO3 gene. Herein, we found 16 variants in the FMO3 coding region, some of which had not been previously documented (Gly38Trp, Asp232Val, Thr307Pro, Ser310Leu). Whenever common variants (Glu158Lys, Glu308Gly) were considered in combination a distinct pattern between the control population and patients was observed, mainly in what concerns the presence of Lys158 and Gly308 in homozygous state. Further studies are necessary to clarify the pathogenicity of novel variants identified in this study, as well as the effect of the common single nucleotide polymorphisms, which may play an important role in disease presentation and/or protective mechanism to xenobiotics drugs or environment.
authors.affiliation: Newborn Screening, Metabolic and Genetics Unit, Department of Human Genetics, National Institute of Health Dr Ricardo Jorge, 4000-055 Porto, Portugal.
authors.forename: Filipa
authors.initials: F
authors.lastname: Ferreira
authors.forename: Sofia
authors.initials: S
authors.lastname: Esteves
authors.forename: Lígia S
authors.initials: LS
authors.lastname: Almeida
authors.forename: Ana
authors.initials: A
authors.lastname: Gaspar
authors.forename: Cláudia Dias
authors.initials: CD
authors.lastname: da Costa
authors.forename: Patrícia
authors.initials: P
authors.lastname: Janeiro
authors.forename: Anabela
authors.initials: A
authors.lastname: Bandeira
authors.forename: Esmeralda
authors.initials: E
authors.lastname: Martins
authors.forename: Elisa Leão
authors.initials: EL
authors.lastname: Teles
authors.forename: Paula
authors.initials: P
authors.lastname: Garcia
authors.forename: Luísa
authors.initials: L
authors.lastname: Azevedo
authors.forename: Laura
authors.initials: L
authors.lastname: Vilarinho
mesh_terms: D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D017124:Conserved Sequence; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D008661:Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics*; D008744:Methylamines / Q000652:urine; D008875:Middle Aged; D020125:Mutation, Missense; D010105:Oxygenases / Q000737:chemistry / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011174:Portugal; D017422:Sequence Analysis, DNA
chemical_list: D008744:Methylamines; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming)
keywords: FMO3; FMO3 gene; Fish odor syndrome; Flavin containing monooxygenase 3 (FMO3); Flavin-containing monooxygenase 3 enzyme; Genetic polymorphisms; MIM; Mendelian Inheritance in Man; N-oxide Trimethylamine; NMR; Novel variants; Nuclear Magnetic Resonance; PCR; Polymerase chain reaction; TMA; TMAO; TMAu; Trimethylamine; Trimethylaminuria; Trimethylaminuria (TMAu); flavin-containing monooxygenase 3 gene