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Immunogenetics

, Volume 59, Issue 12, pp 913–926 | Cite as

The hyper-IgE syndrome is not caused by a microdeletion syndrome

  • Dietmar Pfeifer
  • Cristina Woellner
  • Astrid Petersen
  • Maria Cristina Pietrogrande
  • Josè Luis Franco
  • Mehdi Yeganeh
  • Stephan Ehl
  • Nuria Matamoros
  • Eli Sprecher
  • Jennifer M. Puck
  • Hendrik Veelken
  • Bodo GrimbacherEmail author
Original Paper

Abstract

The hyper-immunoglobulin E syndrome (HIES) is a rare primary immunodeficiency characterized by recurrent infections, elevated serum IgE-levels, and involvement of the soft- and bony tissues. We speculated that this complex disease may be caused by a microdeletion syndrome. We therefore analyzed 30 sporadic HIES patients for the presence of chromosomal imbalances using Affymetrix 50k XbaI and 23 of the 30 patients with the higher-resolution 250k StyI SNP mapping arrays. We detected only eight different copy number alterations in six patients with the 50k approach, and seven of these presented known polymorphic regions not associated with disease. However, one patient showed a unique gain on chromosome 20p. 250k array analysis identified this gain as a rare polymorphism segregating in the patient’s family, but not associated with the HIES phenotype. In addition, 265 known and novel copy number variants (CNVs) were identified with the 250k arrays, but no recurrent imbalances reminescent of a microdeletion syndrome were found. We aligned the identified CNVs with loci that have been associated with HIES or phenotypically overlapping syndromes. Doing so, a 2-Mb deletion spanning the PEPD gene on 19q13.11 was identified on one allele of one patient. Homozygous mutations in PEPD are responsible for the autosomal-recessive prolidase deficiency which resembles HIES in some aspects. Sequencing of the healthy allele, however, revealed a wild-type sequence. In summary, our results suggest that HIES is not likely to be a microdeletion syndrome.

Keywords

Hyper-IgE syndrome Microdeletion syndrome Primary Immunodeficiency SNP-chip analysis PEPD prolidase D 

Notes

Acknowledgments

We thank the patients and their families and Dr. U. Salzer for his help, advice, and the critical reading of the manuscript.

Funding

The work was supported by the Deutsche Forschungsgemeinschaft (DFG) grant GR 1617/3–3.

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Dietmar Pfeifer
    • 1
  • Cristina Woellner
    • 2
  • Astrid Petersen
    • 1
  • Maria Cristina Pietrogrande
    • 3
  • Josè Luis Franco
    • 4
  • Mehdi Yeganeh
    • 5
  • Stephan Ehl
    • 6
  • Nuria Matamoros
    • 7
  • Eli Sprecher
    • 8
  • Jennifer M. Puck
    • 9
  • Hendrik Veelken
    • 1
  • Bodo Grimbacher
    • 2
    • 10
    • 11
    Email author
  1. 1.Department of Hematology and OncologyUniversity Hospital FreiburgFreiburgGermany
  2. 2.Division Rheumatology and Clinical ImmunologyUniversity Hospital FreiburgFreiburgGermany
  3. 3.Department of PediatricsUniversity of Milan, Fondazione Policlinico IRCCSMilanoItaly
  4. 4.Group of Primary ImmunodeficienciesUniversity of AntioquiaMedellínColombia
  5. 5.Immunology, Asthma and Allergy Research Institute, Children Medical CentreTehran University of Medical SciencesTehranIran
  6. 6.Department of Pediatrics and Adolescent MedicineUniversity Hospital FreiburgFreiburgGermany
  7. 7.Servicio de InmunologiaHospital Son DuretaPalma de MallorcaSpain
  8. 8.Department of DermatologyRambam Medical CenterHaifaIsrael
  9. 9.Department of PediatricsUniversity of CaliforniaSan FranciscoUSA
  10. 10.Department of Immunology and Molecular Pathology, Royal Free HospitalUniversity College LondonLondonUK
  11. 11.UCL Immunology ConsortiumRoyal Free Hospital and University College LondonLondonUK

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