Monozygotic Twin Pair Showing Discordant Phenotype for X-linked Thrombocytopenia and Wiskott–Aldrich Syndrome: a Role for Epigenetics?

@article{Buchbinder2011MonozygoticTP,
  title={Monozygotic Twin Pair Showing Discordant Phenotype for X-linked Thrombocytopenia and Wiskott–Aldrich Syndrome: a Role for Epigenetics?},
  author={David K Buchbinder and Kari Christine Nadeau and Diane J Nugent},
  journal={Journal of Clinical Immunology},
  year={2011},
  volume={31},
  pages={773-777}
}
Despite our increasing characterization of the molecular basis for many primary immunodeficiency states, significant heterogeneity in clinical and immunological phenotype exists. Epigenetic alterations have been implicated in the pathogenesis of immune dysregulation and may provide a unique paradigm to help us understand the phenotypic heterogeneity in primary immunodeficiency. The occurrence of X-linked thrombocytopenia (XLT) and Wiskott–Aldrich syndrome (WAS) in monozygotic twins is a rare… 
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References

SHOWING 1-10 OF 34 REFERENCES
Mutations of the Wiskott-Aldrich Syndrome Protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation.
TLDR
By analyzing a large number of patients with WAS/XLT at the molecular level, 5 mutational hotspots in the WASP gene are identified and a strong association between genotype and phenotype is established.
Recent advances in understanding the pathophysiology of Wiskott-Aldrich syndrome.
TLDR
A full understanding of the mechanisms leading to defects in T, B, and dendritic cells still remains poorly understood is still needed to further implement new therapeutic strategies for this peculiar immunodeficiency.
Unique and recurrent WAS gene mutations in Wiskott-Aldrich syndrome and X-linked thrombocytopenia.
TLDR
Mutation screening alone or in combination with analysis of polymorphic loci DXS6940 and DXS255 delineated the germline origin of a unique insertion mutation and four recurrent CpG mutations, three of which arose spontaneously during maternal gametogenesis.
Wiskott-Aldrich syndrome: diagnosis, clinical and laboratory manifestations, and treatment.
Wiskott-Aldrich syndrome: no strict genotype-phenotype correlations but clustering of missense mutations in the amino-terminal part of the WASP gene product
TLDR
An extended homology search revealed a distant relationship of this stretch to the vasodilator-stimulated phosphoprotein (VASP), which is involved in the maintenance of cytoarchitecture by interacting with actin-like filaments.
X-linked thrombocytopenia (XLT) due to WAS mutations: clinical characteristics, long-term outcome, and treatment options.
TLDR
An analysis of the clinical outcome and molecular basis of patients with XLT shows excellent long-term survival but also a high probability of severe disease-related complications, which will allow better decision making when considering treatment options for individual patients withXLT.
Wiskott-Aldrich syndrome/X-linked thrombocytopenia: WASP gene mutations, protein expression, and phenotype.
TLDR
It is concluded that missense mutations affecting the PH domain (exons 1 to 3) of WASP inhibit less important functions of the protein and result in a mild phenotype, and that complex mutations affect the 3' portion of WasP interfere with crucial functions ofThe protein and cause classic WAS.
Clinical course of patients with WASP gene mutations.
TLDR
It is demonstrated that WAS protein expression is a useful tool for predicting long-term prognosis for patients with WAS/XLT and hematopoietic stem cell transplantation should be considered, especially for WASP-negative patients, while the patients are young to improve prognosis.
The epigenetics of autoimmunity
TLDR
Data support the impact of epigenetic changes in systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis and other autoimmune diseases, in some cases based on mechanistical observations.
...
...