Systemic mast cell activation disease (MCAD) comprises disorders characterized by
an enhanced release of mast cell mediators accompanied by a varying accumulation of
dysfunctional mast cells. Within the last years, evidence has been presented that
MCAD is a multifactorial polygenic determined disease with the KITD816V mutation and its induced functional consequences considered as special case. The
respective genes encode proteins for various signaling pathways, epigenetic regulators,
the RNA splicing machinery, and transcription factors. Transgenerational transmission
of MCAD appears to be quite common. The basics of the molecular mechanisms underlying
predisposition of the disease, that is, somatic and germline mutations and the contribution
of epigenetic processes have become identifiable. The aim of the present review is
to present and discuss available genetic, epigenetic and epidemiological findings,
and to present a model of MCAD pathogenesis.
Abbreviations:
MCAD (mast cell activation disease), MCAS (primary mast cell activation syndrome), SM (systemic mastocytosis), miRNA (microRNA), pts (patients), CFS (chronic fatigue syndrome), MITF (microphthalmia-associated transcription factor), mC (5'-methylcytosine), 5hmC (5-hydroxymethylcytosine), NGS (next-generation sequencing), HMC1 (human mast cell leukemia cell line)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: January 11, 2016
Accepted:
January 4,
2016
Received in revised form:
January 2,
2016
Received:
November 23,
2015
Identification
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