, Volume 66, Issue 5, pp 287–297

Evidence for contribution of epigenetic mechanisms in the pathogenesis of systemic mast cell activation disease

  • Britta Haenisch
  • Holger Fröhlich
  • Stefan Herms
  • Gerhard J. Molderings
Original Paper

DOI: 10.1007/s00251-014-0768-3

Cite this article as:
Haenisch, B., Fröhlich, H., Herms, S. et al. Immunogenetics (2014) 66: 287. doi:10.1007/s00251-014-0768-3


Recently, evidence was provided for common familial occurrence of systemic mast cell activation disease (MCAD), i.e., mast cell disorders characterized by aberrant release of mast cell mediators and/or accumulation of pathological mast cells in potentially any tissue. Since there is accumulating evidence that epigenetic processes may have transgenerational consequences, the aim of the present study was to investigate by two different experimental approaches whether epigenetic effects may contribute to the familial occurrence of MCAD. (1) High throughput profiling of the methylation status of the genomic DNA in leukocytes from MCAD patients in comparison to healthy subjects revealed for the first time an association of MCAD with alterations in DNA methylation comprising genes encoding proteins crucially involved in DNA/RNA repair and processing, apoptosis, cell activity, and exocytosis/cell communication. A set of 195 differentially methylated CpG sites could be regarded as candidates for a MCAD signature at the methylation level of the DNA. (2) In a cohort of MCAD patients, a correlation between age at symptom onset and year of birth (reflecting different generations) was observed suggesting the presence of the phenomenon of anticipation. In conclusion, the present findings suggest that epigenetic processes could substantially contribute to the transgenerational transmission of MCAD.


Systemic mast cell activation disease Systemic mastocytosis Systemic mast cell activation syndrome Methylation Anticipation Epigenetics 

Supplementary material

251_2014_768_MOESM1_ESM.pdf (53 kb)
Online Resource Fig. S1Required sample size to detect a twofold change of methylation at Bonferroni corrected p value of 0.05 and statistical power of 80 % (PDF 53 kb)
251_2014_768_MOESM2_ESM.pdf (53 kb)
Online Resource Fig. S2Pedigree of a family with a high familial loading of mast cell activation disease showing anticipation (PDF 53 kb)
251_2014_768_MOESM3_ESM.pdf (53 kb)
Online Resource Fig. S3Sample clustering (Ward’s method) before and after normalization (PDF 53 kb)
251_2014_768_MOESM4_ESM.xls (110 kb)
Online Resource Table S1CpG sites with significantly (adjusted p value <0.05) different methylation between patient and control samples (XLS 110 kb).

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Britta Haenisch
    • 1
    • 2
    • 3
  • Holger Fröhlich
    • 4
  • Stefan Herms
    • 5
    • 6
  • Gerhard J. Molderings
    • 6
  1. 1.German Center for Neurodegenerative Diseases (DZNE)BonnGermany
  2. 2.Federal Institute for Drugs and Medical Devices (BfArM)BonnGermany
  3. 3.Department of PsychiatryUniversity of BonnBonnGermany
  4. 4.Bonn-Aachen International Center for IT (B-IT), Algorithmic BioinformaticsUniversity of BonnBonnGermany
  5. 5.Division of Medical Genetics, University Hospital Basel and Department of BiomedicineUniversity of BaselBaselSwitzerland
  6. 6.Institute of Human GeneticsUniversity Hospital of BonnBonnGermany

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