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Stop codon mutations in the flavin-containing monooxygenase 3 (FMO3) gene responsible for trimethylaminuria in a Japanese population.

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Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/17244

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)

Submitter: 山崎 浩史

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