Comment about the recent TMAU paper involving Professors Phillips and Shephard

We posted in the blog recently about a new research paper on trimethylaminuria in which Professors' Elizabeth Shephard and Ian Phillips were involved. They have kindly given us permission to post a quote about the paper.

The abstract of the paper can be read on pubmed : Relationships between flavin-containing monooxygenase 3 (FMO3) genotype and trimethylaminuria phenotype in a Japanese population

link : Pubmed TMAU paper abstract

Below is the quote given by Professors' Elizabeth Shephard and Ian Phillips about the paper 

Prof Phillips and Shephard : involved with this TMAU paper

1. Of the 13 individuals diagnosed as severe TMAurics are homozygous or compound heterozygous for mutations that severely affect FMO3 function. Given this preponderance of severe mutations, It is likely that the other 3 have unidentified mutations (in promoter or introns) that have a severe affect on expression or processing of FMO3.

2. Most of the TMAurics are classified (on the basis of urinary excretion) as moderate or mild TMAurics. Of these, none is homozygous or compound heterozygous for mutations that severely affect FMO3 activity. This suggests that it is unlikely that these phenotypes are a consequence of unidentified mutations that severely affect expression or activity of FMO3. However, it is possible that some of these individuals have unknown mutations that have moderate effects on expression of the gene or processing of the RNA.

3. Genotype-phenotype correlation: individuals homozygous or compound heterozygous for mutations that have a severe affect on FMO3 activity will suffer from severe TMAU. Therefore, severe TMAU can be diagnosed genetically. However, most TMAurics suffer from moderate or mild forms of the disorder; these cannot be diagnosed genetically and, thus, must be due to factors other than FMO3 genotype. It is likely that exon sequencing would identify only those affected by severe TMAU and, thus, would not be informative for the majority of TMAU sufferers.

4. For the group there is a strong correlation between total urinary TMA (TMA + TMA N-oxide) and the amount excreted as the free amine (TMA), which implies that individuals with moderate or mild TMAU would benefit from a reduction of total TMA load. 

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