11 'self reporting' adult smell patients ? : most have 158 and 308

A new French anecdotal study.
11 adults self-reporting with smells. 

Seems to be a Paris Hospital  Metabolic Testing dept and lab (including psychiatric dept).
They have 13 volunteers.
2 are children with severe TMAU1
11 are 'self-reporting' adults who 'can't be smelt' and all are told they are 'normal' for TMAU (as shown in TMAU urine test result)

But curiously :
Of the 11 adults ...
1 refused testing (why add them to the results ?)
1 did the FMO3 gene test only (they were homo for 158)

so 9 adults did both the DNA and urine test ... (all deemed normal for the urine test)
FMO3 mutations in summary (in the 9 adults that DNA tested)
2 carried (hetero) 158
3 were homo for 158
2 had the combo 158 - 308
2 had no mutation

link to table

FMO3 mutations in 10 'self-reporting' adults

158
158 158 (didn't do urine test)
158 308
no DNA test (refused) ... but - +ve urine test
158-308
158-158
none
158-158
none
158

FMO3 mutations in summary (in the 9 adults that DNA tested)
2 carried (hetero) 158
3 were homo for 158
2 had the combo 158 - 308
2 had no mutation

So only 2/9 had no FMO3 mutation (or none regarded as mutations) in the 532 coding sequence.

E158K , V257M , E308G

FMO3 coding sequence is a 532 amino acid code.
The most common type of 'variant' is a missense, the wrong amino at a codon.
FMO3 has 3 very common missense variants (known as SNP's) :

E158K (at codon 158, E is code for amino, K is code for wrong amino)
V257M (at codon 257)
E308G (at codon 308)

These 3 SNPs are very common :
E158K : maybe 40% carry ?
E308G : maybe 20% carry ?
V257M : maybe 10% carry ?

Given the commonness, they must be relatively mild (to just carry one, or else e.g. 40% of the world would smell).
So these 3 variants are much milder compared to 'severe' mutations.

Back to the paper :
Even though they are common, a curious mind might still find it unusual 158 and 308 showed up so often in the self-reporting adults

9 adults
3 were homo for 158
2 had 158 308 combo
These 5 are a bit unusual
another 2 carry 158 (not too unusual)

The surprise (?) is that only 2/9 carry no FMO3 mutation

Motive of the test :
It seems a psychiatry dept was involved, perhaps leading the study.
Since one adult did no tests, it could be suspected it was a 'psychiatric' initiated study.
Perhaps the 2 kids were added to the study to show what 'real TMAU results' look like.
The 2 kids had smelt to Dr's.
The 11 adults had never smelt to Dr's.

Curiosity 2 :
The 2 kids only 'carried' 153.
TMAU1 is taught as being 'dominant'.
153 is a much rarer mutation, and presumably quite severe.
Both the kids carried another mutation as well as 153, but maybe 153 is the 'sinker'.
One carried 140 (perhaps another severe one).
One carried the common 257.

Hospital metabolic lab papers :
Sadly it's probably a 'drive-by' paper, maybe initiated by the psychiatry dept.
A researcher interested in TMAU would maybe think 'this 158 308 among them is odd and worth more investigation'.
But in this case its probably the end of the road and perhaps the 11 adults will get a ORS diagnosis.

FMO3 consumer testing ?
Its maybe worth seeing if you carry 158, 257 or 308.
Probably all ancestry tests have them in their raw data.
It won't bring you nearer to a diagnosis but adds to the group evidence maybe ??

get New Posts by EMAIL : Enter your email address :

---

A EURORDIS and NORD Member Organization