FLNA Gene - Could a defective gene be part of the problem?

[Granite]

I was fortunate enough to meet a wonderful Geneticist who offered to run a test called Whole Exome Sequencing.  Basically I had a very important part of my genome tested entirely to look for mutations.  Nothing from the test definitively pointed to a mutation being a part of my symptoms or HPPD, but one interesting thing that did show up was a defect in the FLNA gene.

 

Why the defect is so interesting is because out of the companies entire database over 15,000, I'm the only one who has the mutation.  They suggested it could be related to a break-down in a specific protein and may the be the cause of my chronic intestinal inflammation.  It's a neural disorder that causes the inflammation because there's no actual evidence of a blockage.  The esophageal tissue and my skin tissue use the same protein so they could be related...and who knows, maybe ocular tissue?

 

Either way, I thought I'd throw this out there as a idea for those looking for a potential cause.  Because I know no one personally who has HPPD or anyone who has had whole exome sequencing done, I cannot say whether or not this gene is related to the cause of the disease or makes some susceptible to developing it.  But you may want to ask your doctor to find a test that can look for mutations in the FLNA gene and see if you have it also.

 

P.S.  The protein is called Filamin A for anyone who's interested in doing their own research.

 

P.P.S.  Added details about the mutation.

 

DNA Change:  c.1964G>A

 

Position: g.153592952

 

Protein Change:  p.ARG655HIS

 

dbSNIPrsID:  N/A

 

OMIM:  300048

 

Inheritance:  XL

 

Zygosity:  Hemi

 

Classification:  VUS

[VisualDude]

Was testing only the FLNA gene?  Am looking for (and waiting for it to be affordable) whole genome sequencing.  They say it is now under $1000 (which is not affordable) but don't know how/where one could get it done.

[Granite]

Visual!  Hey, bud.  I was actually thinking about you recently, I want to get your opinion on something else, but I need to put it together first.

 

The testing was whole exome sequencing.  It was explained to me that it catches 85% of the genome, the most likely places for defects and such.  I had my test done by Transgenomic, and it was ordered through my geneticist.  At the time, I qualified for a special program they were offering that got me a discount because it was a relatively new database and program.  You can check with them to see if they are still running it, I believe it's under $1,000.

 

The sequencing tests many many more genes.  I actually came up with a couple other unrelated defects.  You can request whether you want to know about all defects or just ones related to your symptoms.

 

My advice is to find a geneticist and have them order through Transgenomic.

[VisualDude]

This is the sort of thing I'm looking for: http://www.nature.com/news/is-the-1-000-genome-for-real-1.14530 .  But it has got to get cheaper, and should, over time - after all "The first sequenced human genome cost nearly $3 billion" so $1000 is a steal if one's got it.  

 

The reason for whole sequencing is to be thorough.  Right now little is known about genes and DNA.  For example, changes in 'junk' areas of DNA affect intelligence - therefore it isn't junk, just not understood yet.  [ http://www.ncbi.nlm.nih.gov/pubmed/24381249 ]  While a whole sequence would not immediately benefit a person, the data is there to review every time something is discovered.  No new testing needed.  Just check the newly understood SNP with what yours is.

 

 

It is notable that you mention HPPD and chronic intestinal inflammation.  While different, I've observed that people with intestinal problems suffer other, seemingly unrelated problems.  This is true with self.  If digestive flow/transit is too slow (>20 hr) whether constipated or not, I feel poorly.  If flow is too fast (< 8 hr), perhaps from eating too many Jalapenos, then I feel poorly.  So it is necessary to ensure a digestive rate in between - which is easy by using stuff like Cascara Sagrada or, since I like Jalapenos - adjust the 'dosage' as needed.  For fast transit time, perhaps something like Blackberry leaf.  My symptom list when transit time is too fast: mainly the feeling of being poisoned.  If too slow: asthma, food sensitivity, irritability, depression, anxiety, fatigue ... its a lot of crap (pun intended) to put up with.  Is vision worse?  Contrast and night vision certainly gets worse.

 

Whether this is 'leaky gut' or something else, it remains to be learned.  But there is a pattern.  Take some time to observe this with others.  For example, does a friend have asthma or food allergies?  What is their digestive transit time (if you can find a polite way to ask them, lol)?

 

 

As a side bar, people with dopamine problems like PD also suffer autonomic nervous system changes.  And its already observed that dopamine issues are involved with HPPD even if it isn't as simple as taking an agonist or antagonist to resolve the problem.  Digesting flow is an autonomic nervous system function - bingo!

[neffbull]

Was testing only the FLNA gene?  Am looking for (and waiting for it to be affordable) whole genome sequencing.  They say it is now under $1000 (which is not affordable) but don't know how/where one could get it done.

https://genesforgood.sph.umich.edu/ I don't know if they provide testing for the FLNA gene but they will analyze your dna and send you the data for free. It is run by the University of Michigan so it's legitimate. https://genesforgood.sph.umich.edu/ FYI, I finish the surveys (took a week) at the end of October, sent the spit sample the second week of november, and after recently talking to them I should receive the results sometime in February (they sent it to the lab Dec 1 and said it takes two months). Once you receive your DNA data upload it to this site https://promethease.com/ondemandagreed