Journal of Clinical Immunology

, Volume 35, Issue 2, pp 168–181 | Cite as

Infectious and Immunologic Phenotype of MECP2 Duplication Syndrome

  • Michael BauerEmail author
  • Uwe Kölsch
  • Renate Krüger
  • Nadine Unterwalder
  • Karin Hameister
  • Fabian Marc Kaiser
  • Aglaia Vignoli
  • Rainer Rossi
  • Maria Pilar Botella
  • Magdalena Budisteanu
  • Monica Rosello
  • Carmen Orellana
  • Maria Isabel Tejada
  • Sorina Mihaela Papuc
  • Oliver Patat
  • Sophie Julia
  • Renaud Touraine
  • Thusari Gomes
  • Kirsten Wenner
  • Xiu Xu
  • Alexandra Afenjar
  • Annick Toutain
  • Nicole Philip
  • Aleksandra Jezela-Stanek
  • Ludwig Gortner
  • Francisco Martinez
  • Bernard Echenne
  • Volker Wahn
  • Christian Meisel
  • Dagmar Wieczorek
  • Salima El-Chehadeh
  • Hilde Van Esch
  • Horst von BernuthEmail author
Original Research


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.


Xq28-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.

Supplementary material

10875_2015_129_MOESM1_ESM.pptx (207 kb)
Supplementary figure 1 Cellular immunological phenotype of patients with MECP2 duplication syndrome. A. Leucocytes. B. Monocytes. C. Neutrophilic leucocytes. D. Eosinophilic leucocytes. E. Basophilic leucocytes. (PPTX 207 kb)
10875_2015_129_MOESM2_ESM.pptx (129 kb)
Supplementary figure 2 Humoral immunological phenotype of patients with MECP2 duplication syndrome. IgG levels against Tetanus toxoid. (PPTX 129 kb)
10875_2015_129_MOESM3_ESM.pptx (65 kb)
Supplementary table 1 Data on duplications of previously non-published patients P11, P14, P16, P18 P19, P23, P24, P25, P26, P28, P29 and P30. (PPTX 64 kb)
10875_2015_129_MOESM4_ESM.pptx (55 kb)
Supplementary table 2 Infectious phenotype of patients with MECP2 duplication syndrome. Pathogens isolated and location of isolation. (PPTX 55 kb)
10875_2015_129_MOESM5_ESM.pptx (81 kb)
Supplementary table 3a Cellular immunological phenotype of patients with MECP2 duplication syndrome. Age group < 6 years and age group 6–10 years. Lymphocyte subsets are depicted in absolute numbers and percentages. Reference values for the respective age group are given. (PPTX 81 kb)
10875_2015_129_MOESM6_ESM.pptx (80 kb)
Supplementary table 3b Cellular immunological phenotype of patients with MECP2 duplication syndrome. Age group 10–18 years and age group >18 years. Lymphocyte subsets are depicted in absolute numbers and percentages. Reference values for the respective age group are given. (PPTX 80 kb)
10875_2015_129_MOESM7_ESM.pptx (66 kb)
Supplementary table 4 Cellular immunological phenotype of patients with MECP2 duplication syndrome. Lymphocyte proliferation assay. Proliferation is depicted as count per minute (cpm). (PPTX 66 kb)


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Michael Bauer
    • 1
    • 25
    Email author
  • Uwe Kölsch
    • 2
  • Renate Krüger
    • 1
  • Nadine Unterwalder
    • 2
  • Karin Hameister
    • 3
  • Fabian Marc Kaiser
    • 4
  • Aglaia Vignoli
    • 5
  • Rainer Rossi
    • 6
  • Maria Pilar Botella
    • 7
  • Magdalena Budisteanu
    • 8
  • Monica Rosello
    • 9
  • Carmen Orellana
    • 9
  • Maria Isabel Tejada
    • 10
  • Sorina Mihaela Papuc
    • 11
  • Oliver Patat
    • 12
  • Sophie Julia
    • 12
  • Renaud Touraine
    • 13
  • Thusari Gomes
    • 14
  • Kirsten Wenner
    • 15
  • Xiu Xu
    • 16
  • Alexandra Afenjar
    • 17
  • Annick Toutain
    • 18
  • Nicole Philip
    • 19
  • Aleksandra Jezela-Stanek
    • 20
  • Ludwig Gortner
    • 14
  • Francisco Martinez
    • 9
  • Bernard Echenne
    • 21
  • Volker Wahn
    • 1
  • Christian Meisel
    • 2
  • Dagmar Wieczorek
    • 22
  • Salima El-Chehadeh
    • 23
  • Hilde Van Esch
    • 24
  • Horst von Bernuth
    • 1
    • 2
    • 25
    Email author
  1. 1.Pediatric Pneumology and ImmunologyCharité University MedicineBerlinGermany
  2. 2.Labor Berlin GmbH, Department of ImmunologyBerlinGermany
  3. 3.Pediatric Neurology and Social Medicine KönigsbornUnnaGermany
  4. 4.Department of Stem Cell Transplantation and Immunology, Children’s HospitalGoethe University HospitalFrankfurt am MainGermany
  5. 5.Epilepsy Center, San Paolo Hospital, Department of Health SciencesUniversity of MilanMilanItaly
  6. 6.Childrens’ Hospital Neukölln, Vivantes GmbHBerlinGermany
  7. 7.Pediatric NeurologyTxagorritxu HospitalVitoria-GasteizSpain
  8. 8.“Prof. Dr. Alexandru Obregia” Clinical Hospital of PsychiatryBucharestRomania
  9. 9.Department of Genetics and prenatal diagnosticsHospital Universitario La FeValènciaSpain
  10. 10.Molecular Genetics Laboratory, Genetics Service, BioCruces Health Research InstituteCruces University HospitalBarakaldoSpain
  11. 11.“Victor Babes” National Institute of PathologyBucharestRomania
  12. 12.Service de génétique médicaleCHU Toulouse - Hôpital PurpanToulouseFrance
  13. 13.Service de génétiqueCHU de Saint-EtienneSaint-EtienneFrance
  14. 14.Department of General Pediatrics and Neonatology, Faculty of MedicineUniversity Children’s Hospital of the SaarlandHomburg/SaarGermany
  15. 15.Children’s University Hospital and Outpatient ClinicHamburg EppendorfGermany
  16. 16.Department of Child HealthcareChildren’s Hospital of Fudan UniversityShanghaiChina
  17. 17.Département de génétiqueCHU Paris-GH La Pitié Salpêtrière Hôpital Pitié-SalpêtrièreParisFrance
  18. 18.Service de génétiqueCHRU de Tours Hôpital BretonneauToursFrance
  19. 19.Unité de génétique clinique, Département de génétique médicaleCHU de Marseille, Hôpital de la TimoneMarseilleFrance
  20. 20.Department of Medical GeneticsThe Children’s Memorial Health InstituteWarsawPoland
  21. 21.Pediatric NeurologyCHU MontpellierMontpellierFrance
  22. 22.Institute of Human GeneticsUniversity Hospital Essen, University of Duisburg-EssenEssenGermany
  23. 23.Centre de GenetiqueHopital d’EnfantsDijonFrance
  24. 24.Center for Human GeneticsUniversity Hospital Leuven, KU LeuvenLeuvenBelgium
  25. 25.Charité – Kinderklinik mit Schwerpunkt Pneumologie und ImmunologieBerlinGermany

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