Genetic testing at tertiary medical center

[RYO]

There seems to numerous posts about patients getting genetic testing with organization such as 23andme but does anyone have experience or recommendations with genetic testing at tertiary medical center (ie Mayo Clinic, Johns Hopkins, Cleveland clinic etc)

Also, are CFS centers such as Stanford/Dr. Montoya or CFI conducting genetic testing on their pool of patients vs "normal" controls?

 

[Valentijn]

Mayo and Cleveland clinics don't take ME/SEID seriously, so it's unlikely that they'd be of much help, especially with sending money outside of their own clinics. More supportive doctors can probably figure out how to request the testing, or provide a referral to a geneticist.

 

[RYO]

I have appointment with geneticist at tertiary center in NC. I was told by Cleveland clinic physician that there are panels of genetic tests that are ordered based upon symptoms and/or suspected pathology. I am hoping for analysis of immune function (ie DICER enzyme mutation), mitochondrial defect, skeletal muscle issue, etc. Any other suggestions?

 

[Pajk]

There is a clinical study being done by NIH through UNC on whole exome sequencing called "NC Genes" . The testing is free. I was able to get into the study via a referral from my neuromuscular doctor. However, they will only sequence genes in your "problem" area (ie neuromuscular/mitochondrial diseases). I learned, through the study, that I was heterozygote for CPT2 mutation which may be the cause of some of my CFS symptoms. Duke is doing the follow up biopsy and cpt2 deletion testing. Duke also informed me about more comprehensive exome sequencing which would test for ALL mutations. However, insurance won't pay for this. Duke did run genetic testing on me for Fabry and this was covered by insurance ( I had very low GLA enzyme, but no mutation).

 

[RYO]

I met with geneticist at UNC last week and he is referring me to exome study. We discussed looking at 3 major areas - muscular, mitochondrial, and immune system. It may take 9-12 months.

In a different thread, I posted about having a muscle ultrasound to indirectly measure glycogen levels. My glycogen levels were very low but I tested negative for Pompe disease via enzyme test. It makes me wonder whether double stranded enteroviral RNA may be interfering with muscle metabolism.

I had muscle biopsy in the past but UNC may perform additional studies.

I certainly believe subset of CFS/ME patients have very prominent muscle symptoms. I am hoping combination of advancements in genetics and new interest in CFS/ME will lead to some answers or at least a direction for further research.

 

[August59]

I certainly believe subset of CFS/ME patients have very prominent muscle symptoms.

From my perspective I'm in complete agreement with this statement

 

[Valentijn]

I learned, through the study, that I was heterozygote for CPT2 mutation which may be the cause of some of my CFS symptoms.

Very interesting. It looks like CPT2 mutations can usually cause little or no problem, until onset of severe problems triggered by infections.

 

[Pajk]

RYO - it took 9 months for me to get the results from NC Genes study. Where did you get muscle ultrasound?

Interestingly, NC Genes did not scan for any immune mutations although my "immune" profile has all been relatively normal. I may follow up with them on this, and am still considering more comprehensive testing through Duke. Because I was in "control" group at NC Genes, they will only share the mutations that may be responsible for my symptoms. I had 7 total mutations in the muscular/mitochondrial area but I have no idea what the other 6 mutations are.

I agree there is likely interaction between illness or injury ( ie stress on body) that interacts with these mutations in subset of Symptomatic people. I also wonder whether multiple mutations can interact to cause disease that alone would be innocuous. Duke had no explanation for why my GLA enzyme was so low. It was the lowest value they had seen for a female who was unaffected by Fabry. Wondering about cofactors involved with CPT 2 and this enzyme.

 

[RYO]

Pajk - muscle ultrasound was performed by sports medicine specialist. It is used typically to optimize performance in athletes. There are small studies measuring skeletal muscle glycogen levels in ICU patients. You can read more information about this technology at www.musclesound.com. I suspect this type of muscle testing will require further validation before wider acceptance.

I also asked geneticist if there was a way to see if mutations exist for DICER enzyme. There was also recent New York Times article about using viral vectors in muscle immune cells to produce desired antibodies. "Protection without a vaccine". It raises interesting questions about whether CFS/ME patients have inability to fight off certain viral infections that are myotropic.

 

[Pajk]

Thanks, RYO. My enzyme test results came back and confirmed I have CPT 2 deficiency. Geneticist believes there is second mutation they haven't uncovered. However, I am in cpt2 support groups and am struggling to find others with adult onset cpt2 who are as severely impacted on a daily basis as myself (although my enzyme levels were very low - unusual for heterozygote). My pancreas enzymes are periodically elevated, my GLA enzyme very low, alkaline phostophase always very low. Just question whether there is more systemic dysfunction happening, from either virus or another mutation.