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Stop codon mutations in the flavin-containing monooxygenase 3 (FMO3) gene responsible for trimethylaminuria in a Japanese population.
Title: | Stop codon mutations in the flavin-containing monooxygenase 3 (FMO3) gene responsible for trimethylaminuria in a Japanese population. |
Authors: | Yamazaki, Hiroshi Browse this author | Fujita, Haruka Browse this author | Gunji, Takaaki Browse this author | Zhang, Jun Browse this author | Kamataki, Tetsuya Browse this author | Cashman, John R. Browse this author | Shimizu, Makiko Browse this author |
Keywords: | Flavin-containing monooxygenase | Fish-like odor syndrome | Trimethylamine | Truncated FMO3 | Japanese | Trimethylaminuria |
Issue Date: | Jan-2007 |
Publisher: | Elsevier Inc. |
Journal Title: | Molecular Genetics and Metabolism |
Volume: | 90 |
Issue: | 1 |
Start Page: | 58 |
End Page: | 63 |
Publisher DOI: | 10.1016/j.ymgme.2006.08.008 |
PMID: | 16996766 |
Abstract: | The reduced capacity of flavin-containing monooxygenase 3 (FMO3) to N-oxidize trimethylamine (TMA) is believed to cause a metabolic disorder. The aim of this study was to investigate the inter-individual variations of FMO3. Genomic DNA of case subjects that showed only 10–20% of FMO3 metabolic capacity among self-reported trimethylaminuria Japanese volunteers was sequenced. Functional analysis of recombinant FMO3 proteins was also performed. One homozygote for a novel single nucleotide substitution causing a stop codon at Arg500 was observed. The biological parents of this Proband A were heterozygous and showed >90% TMA N-oxygenation metabolic capacity. Another Proband B had the Arg500Stop and Cys197Stop codons. The TMA N-oxygenation metabolic capacities of the father and brother of this Proband B were apparently observed by possessing Arg205Cys mutant that coded for decreased TMA N-oxygenase. Recombinant Arg500Stop FMO3 cDNA expressed in Escherichia coli membranes and a series of highly purified truncation mutants at different positions of the C-terminus of FMO3 showed no detectable functional activity toward typical FMO3 substrates. The results suggest that individuals homozygous for either of the nonsense mutations, Arg500Stop and/or Cys197Stop alleles, in the FMO3 gene can possess abnormal TMA N-oxygenation. |
Relation: | http://www.sciencedirect.com/science/journal/10967192 |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/17244 |
Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 山崎 浩史
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