Preti RareC webinar 2013
Monday 27th is cancelled.
Dut to unforeseen circumstance.
NEW DATE CONFIRMED :
THURSDAY 30 MARCH
1pm NYT
TMAU Webinar.
Monday March 27.
1pm EST (New York Time).
Guest Speakers : George Preti and Yiran Guo.
To speak on their recent TMAU paper.
Webinar platform courtesy of RareConnect.
Will be uploaded to YouTube afterwards.
Note : Webinar date/time subject to change, but this is the current agreed time/date.
We will keep you updated.
We are pleased to announce another rareconnect TMAU webinar. The speakers were leaders of the team that published the recent TMAU paper ...
Genetic analysis of impaired trimethylamine metabolism using whole exome sequencing.
Link to full paper
The paper was crowdfunded by the TMAU community via NORD
Link to full paper
The paper was crowdfunded by the TMAU community via NORD
Guest Speakers :
George Preti (Monell Chemical Senses Center. Philadelphia)
Yiran Guo (Geneticist, Children's Hospital of Philadelphia)
The recent TMAU paper was interesting as it implied that genetic TMAU may not be solely due to faults in the FMO3 enzyme, but may also sometimes involve other enzymes.
RareConnect
RareConenct is a European charity that provides forums and networking for rare disorders. They have long been a help to the TMAU community, and hosted a few TMAU webinars before. This webinar will kindly be hosted by rareconnect staff member Marta.
rareconnect TMAU forum
Abstract of paper :
Abstract
BACKGROUND:
Trimethylaminuria (TMAU) is a genetic disorder whereby people cannot convert trimethylamine (TMA) to its oxidized form (TMAO), a process that requires the liver enzyme FMO3. Loss-of-function variants in the FMO3 gene are a known cause of TMAU. In addition to the inability to metabolize TMA precursors like choline, patients often emit a characteristic odor because while TMAO is odorless, TMA has a fishy smell. The Monell Chemical Senses Center is a research institute with a program to evaluate people with odor complaints for TMAU.
METHODS:
Here we evaluated ten subjects by (1) odor evaluation by a trained sensory panel, (2) analysis of their urine concentration of TMA relative to TMAO before and after choline ingestion, and (3) whole exome sequencing as well as subsequent variant analysis of all ten samples to investigate the genetics of TMAU.
RESULTS:
While all subjects reported they often emitted a fish-like odor, none had this malodor during sensory evaluation. However, all were impaired in their ability to produce >90% TMAO/TMA in their urine and thus met the criteria for TMAU. To probe for genetic causes, the exome of each subject was sequenced, and variants were filtered by genes with a known (FMO3) or expected effect on TMA metabolism function (other oxidoreductases). We filtered the remaining variants by allele frequency and predicated functional effects. We identified one subject that had a rare loss-of-function FMO3 variant and six with more common decreased-function variants. In other oxidoreductases genes, five subjects had four novel rare single-nucleotide polymorphisms as well as one rare insertion/deletion. Novel in this context means no investigators have previously linked these variants to TMAU although they are in dbSNP.
CONCLUSIONS:
Thus, variants in genes other than FMO3 may cause TMAU and the genetic variants identified here serve as a starting point for future studies of impaired TMA metabolism.
Abstract
BACKGROUND:
Trimethylaminuria (TMAU) is a genetic disorder whereby people cannot convert trimethylamine (TMA) to its oxidized form (TMAO), a process that requires the liver enzyme FMO3. Loss-of-function variants in the FMO3 gene are a known cause of TMAU. In addition to the inability to metabolize TMA precursors like choline, patients often emit a characteristic odor because while TMAO is odorless, TMA has a fishy smell. The Monell Chemical Senses Center is a research institute with a program to evaluate people with odor complaints for TMAU.
METHODS:
Here we evaluated ten subjects by (1) odor evaluation by a trained sensory panel, (2) analysis of their urine concentration of TMA relative to TMAO before and after choline ingestion, and (3) whole exome sequencing as well as subsequent variant analysis of all ten samples to investigate the genetics of TMAU.
RESULTS:
While all subjects reported they often emitted a fish-like odor, none had this malodor during sensory evaluation. However, all were impaired in their ability to produce >90% TMAO/TMA in their urine and thus met the criteria for TMAU. To probe for genetic causes, the exome of each subject was sequenced, and variants were filtered by genes with a known (FMO3) or expected effect on TMA metabolism function (other oxidoreductases). We filtered the remaining variants by allele frequency and predicated functional effects. We identified one subject that had a rare loss-of-function FMO3 variant and six with more common decreased-function variants. In other oxidoreductases genes, five subjects had four novel rare single-nucleotide polymorphisms as well as one rare insertion/deletion. Novel in this context means no investigators have previously linked these variants to TMAU although they are in dbSNP.
CONCLUSIONS:
Thus, variants in genes other than FMO3 may cause TMAU and the genetic variants identified here serve as a starting point for future studies of impaired TMA metabolism.
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1 comments:
I congratulate and thank this research that will help so many people. If there are other genetic sources for this damn disease they have to be investigated in order to discover possible cures.