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A novel immunodeficiency syndrome associated with partial trisomy 19p13
  1. Markus G Seidel1,
  2. Celia Duerr2,
  3. Stavroula Woutsas3,
  4. Anette Schwerin-Nagel4,
  5. Kambis Sadeghi2,
  6. Jürgen Neesen5,
  7. Sabine Uhrig6,
  8. Elisangela Santos-Valente3,
  9. Winfried F Pickl7,
  10. Wolfgang Schwinger1,
  11. Christian Urban1,
  12. Kaan Boztug2,3,
  13. Elisabeth Förster-Waldl2
  1. 1Divison of Pediatric Hematology-Oncology, Department Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria
  2. 2Divison of Neonatology, Paediatric Intensive Care & Neuropaediatrics, Department Paediatrics and Adolescent Medicine, Medical University Vienna, Vienna, Austria
  3. 3CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
  4. 4Divison of General Pediatrics, Department Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria
  5. 5Institute of Medical Genetics, Medical University of Vienna, Vienna, Austria
  6. 6Institute of Human Genetics, Medical University Graz, Graz, Austria
  7. 7Institute of Immunology, Medical University of Vienna, Vienna, Austria
  1. Correspondence to Kaan Boztug, M.D., CeMM Research Center for Molecular Medicine, Lazarettgasse 14, AKH BT 25.3, 1090 Vienna, Austria; kboztug@cemm.oeaw.ac.at; Elisabeth Förster-Waldl, M.D., Division of Neonatology, Paediatric Intensive Care & Neuropaediatrics, Department of Paediatrics and Adolescent Medicine, Medical University Vienna, Währinger Gürtel 18–20; 1090 Vienna, Austria; Elisabeth.foerster-waldl@ meduniwien.ac.at; Markus G. Seidel, M.D., Division of Pediatric Hematology-Oncology, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Austria, Auenbruggerpl. 38; 8036 Graz, Austria; markus.seidel@medunigraz.at

Abstract

Background Subtelomeric deletions and duplications may cause syndromic disorders that include features of immunodeficiency. To date, no phenotype of immunological pathology has been linked to partial trisomy 19. We report here on two unrelated male patients showing clinical and laboratory signs of immunodeficiency exhibiting a duplication involving Chromosome 19p13.

Methods Both patients underwent a detailed clinical examination. Extended laboratory investigations for immune function, FISH and array comparative genome hybridization (CGH) analyses were performed.

Results The reported patients were born prematurely with intrauterine growth retardation and share clinical features including neurological impairment, facial dysmorphy and urogenital malformations. Array CGH analyses of both patients showed a largely overlapping terminal duplication affecting Chromosome 19p13. In both affected individuals, the clinical course was marked by recurrent severe infections. Signs of humoral immunodeficiency were detected, including selective antibody deficiency against polysaccharide antigens in patient 1 and reduced IgG1, IgG3 subclass levels and IgM deficiency in patient 2. Class-switched B memory cells were almost absent in both patients. Normal numbers of T cells, B cells and natural killer cells were observed in both boys. Lymphocytic proliferation showed no consistent functional pathology, however, function of granulocytes and monocytes as assessed by oxidative burst test was moderately reduced. Moreover, natural killer cytotoxicity was reduced in both patients. Immunoglobulin substitution resulted in a decreased number and severity of infections and improved thriving in both patients.

Conclusions Partial trisomy 19p13 represents a syndromic disorder associating organ malformation and hitherto unrecognised immunodeficiency.

  • syndrome with primary immunodeficiency (PID)
  • hypogammaglobulinemia
  • subtelomeric microduplication and microdeletion
  • 19p
  • array CGH

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