Infectious and Immunologic Phenotype of MECP2 Duplication Syndrome
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MECP2 (methyl CpG binding protein 2) duplication causes syndromic intellectual disability. Patients often suffer from life-threatening infections, suggesting an additional immunodeficiency. We describe for the first time the detailed infectious and immunological phenotype of MECP2 duplication syndrome. 17/27 analyzed patients suffered from pneumonia, 5/27 from at least one episode of sepsis. Encapsulated bacteria (S.pneumoniae, H.influenzae) were frequently isolated. T-cell immunity showed no gross abnormalities in 14/14 patients and IFNy-secretion upon ConA-stimulation was not decreased in 6/7 patients. In 6/21 patients IgG2-deficiency was detected – in 4/21 patients accompanied by IgA-deficiency, 10/21 patients showed low antibody titers against pneumococci. Supra-normal IgG1-levels were detected in 11/21 patients and supra-normal IgG3-levels were seen in 8/21 patients – in 6 of the patients as combined elevation of IgG1 and IgG3. Three of the four patients with IgA/IgG2-deficiency developed multiple severe infections. Upon infections pronounced acute-phase responses were common: 7/10 patients showed CRP values above 200 mg/l. Our data for the first time show systematically that increased susceptibility to infections in MECP2 duplication syndrome is associated with IgA/IgG2-deficiency, low antibody titers against pneumococci and elevated acute-phase responses. So patients with MECP2 duplication syndrome and low IgA/IgG2 may benefit from prophylactic substitution of sIgA and IgG.
KeywordsXq28-duplication syndrome methyl CpG binding protein 2 (MECP2) MECP2 duplication syndrome primary immunodeficiency intellectual disability humoral immunodeficiency
Methyl CpG binding protein 2
X linked intellectual disability
We thank the patients and their families for participating in this study and Margret Oberreit, Petra Ellensohn (deceased 01/2011), Christine Seib, Kristin Neuhaus, Anne-Hélène Lebrun and Karoline Strehl for discussions, critical reading of the manuscript and technical assistance. This work was supported by the German Research Foundation (DFG BE 3895/3-1), the Federal Ministry of Education and Research, Germany (BMBF PID-NET 01GM1111D/TP-A5) and the Sonnenfeld Stiftung, Berlin.
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