Two novel mutations of theFMO3 gene in a proband with trimethylaminuria

Akerman, Beverly R.; Forrest, Susan M.; Chow, Li Hui; Youil, Rima; Knight, Melanie A.; Treacy, Eileen

doi:10.1002/(sici)1098-1004(1999)13:5<376::aid-humu5>3.0.co;2-a

Cited by 38 publications

(11 citation statements)

References 15 publications

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“…Similar nonsense mutations in humans (E305X, E314X) have been shown to lead to a complete loss of enzyme activity (Treacy et al 1998;Akerman et al 1999). Moreover, we ob- Culbertson 1999).…”

Section: Discussionmentioning

confidence: 63%

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A Nonsense Mutation in the FMO3 Gene Underlies Fishy Off-Flavor in Cow's Milk

Lundén

Marklund²,

Gustafsson³

et al. 2002

Genome Res.

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Fish-odor syndrome or Trimethylaminuria (OMIM #602079) in humans is an inborn error of metabolism associated with a characteristic fishy body odor due to elevated levels of trimethylamine (TMA) in body fluids. It is caused by loss-of-function mutations in FMO3encoding flavin-containing mono-oxygenase 3. A fishy off-flavor is occasionally observed in cow's milk and it has been established recently that this phenotype is due to elevated TMA levels. Here, we report that fishy off-flavor in cow's milk is caused by a nonsense mutation (R238X) in the bovine FMO3 ortholog. RT–PCR analysis indicated that the mutant transcript is present in a very low amount. The mutation was found to be surprisingly common (q = 0.155) in one breed of cattle.[The sequence data described in this paper have been submitted to GenBank with accession nos.AF488417–AF488422. The following individuals kindly provided reagents, samples, or unpublished information as indicated in the paper: K. Sandberg and I. Hansson.]

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Section: Discussionmentioning

confidence: 63%

“…The fishy odor is a consequence of impaired oxidation of TMA (Spellacy et al 1980). The fish-odor syndrome in humans is due to loss-of-function mutations in FMO3 encoding an isoform of flavin-containing mono-oxygenase (Dolphin et al 1997;Treacy et al 1998;Akerman et al 1999;Basarab et al 1999;Forrest et al 2001).…”

mentioning

confidence: 99%

A Nonsense Mutation in the FMO3 Gene Underlies Fishy Off-Flavor in Cow's Milk

Lundén

Marklund²,

Gustafsson³

et al. 2002

Genome Res.

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“…The dietary material TMA, arising from choline and other sources, is exclusively N-oxygenated by human FMO3 and provides a selective functional biomarker of FMO3 enzyme activity. In humans, it was noted that abnormal TMA metabolism was directly correlated with genetic variation of the FMO3 gene (Treacy et al, 1998;Akerman et al, 1999;Dolphin et al, 2000). Variation in the human FMO3 gene arises from SNPs that can lead to alteration of enzyme function (Cashman, 2002).…”

Section: Discussionmentioning

confidence: 99%

TWO NEW POLYMORPHISMS OF THE FMO3 GENE IN CAUCASIAN AND AFRICAN-AMERICAN POPULATIONS: COMPARATIVE GENETIC AND FUNCTIONAL STUDIES

Lattard¹,

Zhang²,

Tran³

et al. 2003

Drug Metab Dispos

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“…Individuals diagnosed with trimethylaminuria have a decrease in FMO3 enzyme activity [18,[115][116][117][118][119][120][121][122][123][124][125][126][127][128] and a database has been established to maintain information on human FMO3 variants [129]. Currently, twenty-four missense, three nonsense, and one gross deletion mutation have been reported in the database [129].…”

Section: Gene Responsible For Expression Of Fmo3 Enzymementioning

confidence: 99%

Trimethylamine: Metabolic, Pharmacokinetic and Safety Aspects

Bain¹,

Fornasini²,

Evans

2005

CDM

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Trimethylamine (TMA) is a volatile tertiary aliphatic amine that is derived from the diet either directly from the consumption of foods containing TMA, or by the intake of food containing precursors to TMA such as trimethylamine-N-oxide (TMNO), choline and L-carnitine. Following oral absorption in humans, TMA undergoes efficient N-oxidation to TMNO, a reaction catalyzed by the flavin-containing monooxygenase (FMO) isoform 3 enzyme. TMNO subsequently undergoes excretion in the urine, although, evidence also suggests that metabolic retro-reduction of TMNO can occur. Whilst the pharmacokinetics of TMA and TMNO has not been fully elucidated in humans, a number of studies provide information on the likely fate of dietary derived TMA. Trimethylaminuria is a condition that is characterized by a deficiency in FMO3 enzyme activity, resulting in the excretion of increased amounts of TMA in bodily fluids such as urine and sweat, and breath. A human FMO3 database has been established and currently twenty-eight variants of the FMO3 gene have been reported including twenty-four missense, three nonsense, and one gross deletion mutation. Whilst TMA and TMNO are generally regarded as non-toxic substances, they are of clinical interest because of their potential to form the carcinogen N-nitrosodimethylamine.

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Two novel mutations of theFMO3 gene in a proband with trimethylaminuria

Cited by 38 publications

References 15 publications

A Nonsense Mutation in the FMO3 Gene Underlies Fishy Off-Flavor in Cow's Milk

A Nonsense Mutation in the FMO3 Gene Underlies Fishy Off-Flavor in Cow's Milk

TWO NEW POLYMORPHISMS OF THE FMO3 GENE IN CAUCASIAN AND AFRICAN-AMERICAN POPULATIONS: COMPARATIVE GENETIC AND FUNCTIONAL STUDIES

Trimethylamine: Metabolic, Pharmacokinetic and Safety Aspects

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