Structural Organization of the Human Flavin-Containing Monooxygenase 3 Gene (FMO3), the Favored Candidate for Fish-Odor Syndrome, Determined Directly from Genomic DNA

Abstract

The inherited metabolic disorder trimethylaminuria (fish-odor syndrome) is associated with defective hepaticN-oxidation of dietary-derived trimethylamine catalyzed by flavin-containing monooxygenase (FMO). AsFMO3encodes the major form of FMO expressed in adult human liver, it represents the best candidate gene for the disorder. The structural organization ofFMO3was determined by sequencing the products of exon-to-exon and vectorette PCR, the latter through the use of vectorette libraries constructed directly from genomic DNA. The gene contains one noncoding and eight coding exons. Knowledge of the exon / intron organization of the humanFMO3gene enabled each of the coding exons of the gene, together with their associated flanking intron sequences, to be amplified from genomic DNA and will thus facilitate the identification of mutations inFMO3in families affected with fish-odor syndrome.