Missense and Nonsense Mutations of the Flavin-containing Monooxygenase 3 Gene in a Japanese Cohort

Abstract

  We sequenced all exons and exon-intron junctions of the flavin-containing monooxygenase 3 (FMO3) gene from 3 Japanese individuals and their family members, who were case subjects that showed low FMO3 metabolic capacity among a population of self-reported trimethylaminuria Japanese volunteers (n=50). We found three novel single nucleotide polymorphisms (SNPs) (g. 20752 A>G, g. 27400 G>A, and g. 30308 C>T) causing an amino acid substitution and stop codons, Asn¹¹⁴Ser in exon 4, Trp³⁸⁸Stop in exon 7, and Gln⁴⁷⁰Stop in exon 9, respectively. The Trp³⁸⁸Stop and Gln⁴⁷⁰Stop also presented together with known SNPs, Val²⁵⁷Met and Glu¹⁵⁸Lys, respectively, in the same alleles of the FMO3 gene to form novel haplotypes.
   These sequences are as follows:
  1) SNP, 060825Shimizu004; GENE NAME, FMO3; ACCESSION NUMBER, AL021026; LENGTH, 25 base; 5′-TATCCAGTGTAAA/GTAAACATCCTGA-3′.
  2) SNP, 060825Shimizu005; GENE NAME, FMO3; ACCESSION NUMBER, AL021026; LENGTH, 25 base; 5′-CCAGTCCCGCTGG/AGCAGCACAAGTA-3′.
  3) SNP, 060825Shimizu006; GENE NAME, FMO3; ACCESSION NUMBER, AL021026; LENGTH, 25 base; 5′-TGTAGTCCCTACC/TAGTTTAGGCTGG-3′.