oh man, this is FASCINATING -- a genetic link: duplication or triplication of a gene called TPSAB1, which leads to high tryptase levels.
Mental Floss reported on it yesterday
here.
"The latest study, led by Joshua Milner at the National Institute of Allergy and Infectious Diseases, involved 96 people with EDS-HT and mast cell issues. POTS symptoms were common, especially gut problems like Irritable Bowel Syndrome.
The study participants had another thing in common: higher-than-normal levels of a protein called tryptase in their blood. Tryptase is part of the immune system’s reaction and has been linked to a handful of core EDS-HT and POTS symptoms, Milner says.
"Tryptase can contribute to pain sensitivity," he told me. "It can contribute to blood vessels doing funny things, and it can contribute to how your connective tissue, your bones and joints, are made."
Most people with mast cell issues actually have normal levels of tryptase, so the group Milner and his colleagues tested represented just a small subset of mast cell patients. But that subset did seem to have a unique genetic signature: an extra copy of a gene called TPSAB1. Under normal circumstances, TPSAB1 makes a form of tryptase called alpha-tryptase. People with a double dose of the gene are getting a double dose of the protein, too."
The article is available at nature.com
here"Elevated basal serum tryptase levels are present in 4–6% of
the general population, but the cause and relevance of such
increases are unknown. Previously, we described subjects
with dominantly inherited elevated basal serum tryptase levels
associated with multisystem complaints including cutaneous
flushing and pruritus, dysautonomia, functional gastrointestinal
symptoms, chronic pain, and connective tissue abnormalities,
including joint hypermobility. Here we report the identification
of germline duplications and triplications in the TPSAB1 gene
encoding a-tryptase that segregate with inherited increases
in basal serum tryptase levels in 35 families presenting with
associated multisystem complaints. Individuals harboring alleles
encoding three copies of a-tryptase had higher basal serum levels
of tryptase and were more symptomatic than those with alleles
encoding two copies, suggesting a gene-dose effect. Further, we
found in two additional cohorts (172 individuals) that elevated
basal serum tryptase levels were exclusively associated with
duplication of a-tryptase–encoding sequence in TPSAB1, and
affected individuals reported symptom complexes seen in our
initial familial cohort. Thus, our findings link duplications in
TPSAB1 with irritable bowel syndrome, cutaneous complaints,
connective tissue abnormalities, and dysautonomia"
table one? is me except for the beighton score (i was dxed with eds in 72, before the beighton scale was developed) and i had only a "poor man's tilt table test", which was positive.
i found the compass-31 scale online and took it -- raw 51.5, weighted 70.1. i couldn't find a reference scale, but i'mpretty sure that's more than a bit high.
i am FASCINATED by this. so much so that i emailed one of the authors askingif SNPs had been identified that i could look up in my autosomal dna results.
