A compound heterozygous mutation in the FMO3 gene: the first pediatric case causes fish odor syndrome in Korea / 소아과

Trimethylaminuria (TMAuria), known as “fish odor syndrome,” is a congenital metabolic disorder characterized by an odor resembling that of rotting fish. This odor is caused by the secretion of trimethylamine (TMA) in the breath, sweat, and body secretions and the excretion of TMA along with urine. TMAuria is an autosomal recessive disorder caused by mutations in flavin-containing monooxygenase 3 (FMO3). Most TMAuria cases are caused by missense mutations, but nonsense mutations have also been reported in these cases. Here, we describe the identification of a novel FMO3 gene mutation in a patient with TMAuria and her family. A 3-year-old girl presented with a strong corporal odor after ingesting fish. Genomic DNA sequence analysis revealed that she had compound heterozygous FMO3 mutations; One mutation was the missense mutation p.Val158Ile in exon 3, and the other was a novel nonsense mutation, p.Ser364X, in exon 7 of the FMO3 gene. Familial genetic analyses showed that the p.Val158Ile mutation was derived from the same allele in the father, and the p.Ser364X mutation was derived from the mother. This is the first description of the p.Ser364X mutation, and the first report of a Korean patient with TMAuria caused by novel compound heterozygous mutations.

Relationship between the flavin-containing monooxygenase 3 gene polymorphisms and the liver injury caused by methimazole / 中国药学杂志

OBJECTIVE: To explore the relationship between the flavin-containing monooxygenase 3 gene polymorphisms and the liver injury caused by methimazole in the Chinese Han patients with GD in Shandong area.

Plasma Concentrations of Clozapine and its Metabolites and FMO3 Variations in Korean Schizophrenic Patients

OBJECTIVE: The relationship between the total daily dose of clozapine given and the plasma concentrations of clozapine and its metabolites(N-desmethylclozapine and clozapine N-oxide) and the effect of Glu158Lys (wild-type: Glu, 'H' ; variant: Lys, 'h') and Glu308Gly(wild-type: Glu, 'D' ; variant: Lys, 'd') variation in FMO3 gene on plasma concentrations of clozapine and its metabolites was studied in schizophrenic patients. METHODS: Trough plasma concentrations of clozapine and its metabolites were measured in 34 schizophrenic patients receiving clozapine. The genetic variation of 'h' and 'd' in FMO3 were analyzed in 21 among 34 patients. RESULTS: A linear relationship between the total daily dose of clozapine given(mg/kg body weight per day) and the plasma concentrations(nM) of clozapine was revealed by regression analysis(p<0.001) in the 23 patients receiving a constant daily dose of clozapine for 8 days. The plasma molar concentration ratios of clozapine N-oxide/clozapine in 8 subjects with 'hh' or 'Hh' alleles were not different from those in 6 subjects with 'HH' alleles and the plasma molar concentration ratios in 6 subjects with 'dd' or 'Dd' alleles were not different from those in 8 subjects with 'DD' alleles. CONCLUSION: The effect of Glu158Lys and Glu308Gly variation in FMO3 gene on clozapine metabolism could not be shown.