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http://mastcelldisorders.wallack.us/yabb/YaBB.pl New Mast Cell Research, Studies, and Trials >> New Mast Cell Research, Studies, and Trials >> The genetic basis of mast cell activation disease http://mastcelldisorders.wallack.us/yabb/YaBB.pl?num=1412375369 Message started by Spartako on 10/03/14 at 11:29:29

Title: The genetic basis of mast cell activation disease
Post by Spartako on 10/03/14 at 11:29:29

The genetic basis of mast cell activation disease - looking through a glass darkly
Gerhard J. Molderings
http://www.croh-online.com/article/S1040-8428%2814%2900149-8/fulltext

Within the last decade, and in particular since 2012, research has greatly extended our understanding of the molecular basis of systemic mast cell activation disease (MCAD). Initial studies demonstrated that somatic mutations in the tyrosine kinase KIT led to the establishment of a clonal mast cell population. Recent studies, in particular those involving next generation sequencing analyses of advanced systemic mastocytosis, have revealed mutations in additional genes. The respective genes encode proteins for various signaling pathways, epigenetic regulators, the RNA splicing machinery, and transcription factors. Although almost all of the detected mutations are somatic in nature, transgenerational transmission of MCAD appears to be quite common. However, the molecular mechanisms underlying genetic predestination, e.g. germline mutations and the contribution of epigenetic processes, still await identification. In the present review available genetic findings are presented and discussed, and the relationship between adult-onset systemic MCAD and childhood-onset mastocytosis, often termed cutaneous mastocytosis, is outlined on the basis of current genetic data. Finally, the implications of increased knowledge of the molecular basis of MCAD in terms of diagnostics and therapy are discussed.