Two novel mutations of the FMO3 gene in a proband with trimethylaminuria

The mammalian flavin-containing monooxygenases catalyze the NADPH dependent N-oxygenation of nucleophilic nitrogen-, sulfur-, and phosphorus-containin g chemicals, drugs, and xenobiotics, in eluding trimethylamine. The FMO3 ge ne encodes the dominant catalytically active isoform present in human liver . We have identified two missense mutations in the coding region of the gen e in a proband with trimethylaminuria (TMA): M66I and R492W. Whereas two mu tations (P153L, E305X) accounted for TMA in our eight unrelated previously documented Australian families of British origin, the present report is the first evidence of compound heterozygosity for two rare mutations in a prob and with this disorder. This suggests that other rarer alleles, also causin g TMA, will be found in the same populations. Hum Mutat 13:376-379, 1999. ( C) 1999 Wiley Liss, Inc.