title: Combined immunodeficiency in a patient with mosaic monosomy 21.
abstract: Monosomy 21 is an extremely rare genetic disorder presenting with a wide array of symptoms. Recurrent infections, some life threatening, have been reported in several monosomy 21 patients and attributed to an, as of yet, undefined immunodeficiency. Here we report on a 3-year-old boy with mosaic monosomy 21 who presented with clinical and laboratory evidence of immunodeficiency. Despite suffering from infections highly suggestive of a cell-mediated immune defect, the patient's T cells displayed normal counts, subsets and proliferation capability. T cell receptor repertoire was diverse, and de novo T cell production was intact. Consistent with earlier case reports, our patient displayed mildly low B cell counts with hypogammaglobulinemia. B cell subsets demonstrated mainly naïve and marginal zone B cells that have not undergone class switch. Subsequently, IgG, IgA and IgE levels were near absent, whereas IgM level was normal. De novo B cell production and B cell receptor diversity were normal. Together, these results are indicative of a defect in immunoglobulin class switching as the principal cause of immunodeficiency in monosomy 21. A better understanding of the immunodeficiency in this syndrome will enable targeted treatment and prevention of infections in order to prevent morbidity and mortality in these patients.
authors.affiliation: Pediatric Department A and the Immunology Service, "Edmond and Lily Safra" Children's Hospital, Jeffrey Modell Foundation Center, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Erez
authors.initials: E
authors.lastname: Rechavi
authors.affiliation: Pediatric Department A and the Immunology Service, "Edmond and Lily Safra" Children's Hospital, Jeffrey Modell Foundation Center, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Sarina
authors.initials: S
authors.lastname: Levy-Mendelovich
authors.affiliation: Pediatric Department A and the Immunology Service, "Edmond and Lily Safra" Children's Hospital, Jeffrey Modell Foundation Center, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Tali
authors.initials: T
authors.lastname: Stauber
authors.affiliation: Institute of Rare Diseases, Institute of Genetics Sheba Medical Center, Tel Hashomer & Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Jana
authors.initials: J
authors.lastname: Shamash
authors.affiliation: The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Shlomit
authors.initials: S
authors.lastname: Reinstein
authors.affiliation: Hematology Laboratories, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Helly
authors.initials: H
authors.lastname: Vernitsky
authors.affiliation: Pediatric Department, Meir Medical Center, Sackler School of Medicine, Tel-Aviv University, Kfar-Saba, Israel.
authors.forename: Dganit
authors.initials: D
authors.lastname: Adam
authors.affiliation: Pediatric Department A and the Immunology Service, "Edmond and Lily Safra" Children's Hospital, Jeffrey Modell Foundation Center, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.|Hematology Laboratories, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Amos J
authors.initials: AJ
authors.lastname: Simon
authors.affiliation: Pediatric Department A and the Immunology Service, "Edmond and Lily Safra" Children's Hospital, Jeffrey Modell Foundation Center, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Atar
authors.initials: A
authors.lastname: Lev
authors.affiliation: Institute of Rare Diseases, Institute of Genetics Sheba Medical Center, Tel Hashomer & Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Annick
authors.initials: A
authors.lastname: Raas-Rothschild
authors.affiliation: Pediatric Department A and the Immunology Service, "Edmond and Lily Safra" Children's Hospital, Jeffrey Modell Foundation Center, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. rsomech@hotmail.com.
authors.forename: Raz
authors.initials: R
authors.lastname: Somech
mesh_terms: D000361:Agammaglobulinemia / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology*; D002675:Child, Preschool; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics; D007153:Immunologic Deficiency Syndromes / Q000175:diagnosis / Q000235:genetics*; D007156:Immunologic Memory; D007239:Infections / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D009006:Monosomy / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*
keywords: Class switch; Hypogammaglobulinemia; Immunodeficiency; KREC; Monosomy 21; TREC