Our previous demonstration that a mutation, P153L (C to T), in the FMO3 gene segregated with the disorder and inactivated the enzyme confirmed that defects in FMO3 underlie the inherited form of fish-odour syndrome.
Structural organization of the human flavin-containing monooxygenase 3 gene (FMO3), the favored candidate for fish-odor syndrome, determined directly from genomic DNA.
Herein, we describe data to support the proposal that menses can be an additional factor causing transient trimethylaminuria in self-reported subjects suffering from malodor and even in healthy women harboring functionally active flavin-containing monooxygenase 3 (FMO3).
Genomic DNA of case subjects that showed only 10-20% of FMO3 metabolic capacity among self-reported trimethylaminuria Japanese volunteers was sequenced.
Our results indicate that defects in FMO3 underlie fish-odour syndrome and that the Pro 153-->Leu 153 mutation described here is a cause of this distressing condition.
Rare variants that severely affect production or activity of FMO3 cause the disorder trimethylaminuria and impair metabolism of drug substrates of FMO3.
Our previous demonstration that a mutation, P153L (C to T), in the FMO3 gene segregated with the disorder and inactivated the enzyme confirmed that defects in FMO3 underlie the inherited form of fish-odour syndrome.
The subjects were 640 Japanese volunteers with self-reported trimethylaminuria; genomic DNA was sequenced in those that had 10-70% FMO3 metabolic capacity in urine tests.
Certain mutations within the hFMO3 gene cause defective trimethylamine (TMA) N-oxygenation leading to trimethylaminuria (TMAU) also known as fish-odour syndrome.
Trimethylaminuria is caused by excessive malodorous trimethylamine excreted via urine and body secretion by decreased hepatic flavin-containing monooxygenase 3 (FMO3) metabolic capacity for transforming non-odorous trimethylamine N-oxide.
Leu153 has been reported previously as a homozygous mutation in two unrelated siblings with trimethylaminuria and has been shown to result in total loss of FMO3 enzyme activity.