title: A novel immunodeficiency syndrome associated with partial trisomy 19p13.
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.
authors.affiliation: Divison of Pediatric Hematology-Oncology, Department Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria.
authors.forename: Markus G
authors.initials: MG
authors.lastname: Seidel
authors.forename: Celia
authors.initials: C
authors.lastname: Duerr
authors.forename: Stavroula
authors.initials: S
authors.lastname: Woutsas
authors.forename: Anette
authors.initials: A
authors.lastname: Schwerin-Nagel
authors.forename: Kambis
authors.initials: K
authors.lastname: Sadeghi
authors.forename: Jürgen
authors.initials: J
authors.lastname: Neesen
authors.forename: Sabine
authors.initials: S
authors.lastname: Uhrig
authors.forename: Elisangela
authors.initials: E
authors.lastname: Santos-Valente
authors.forename: Winfried F
authors.initials: WF
authors.lastname: Pickl
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schwinger
authors.forename: Christian
authors.initials: C
authors.lastname: Urban
authors.forename: Kaan
authors.initials: K
authors.lastname: Boztug
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Förster-Waldl
mesh_terms: D001323:Autoantibodies / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D056724:Immunity, Humoral / Q000235:genetics; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010641:Phenotype; D011247:Pregnancy; D014314:Trisomy / Q000235:genetics*
chemical_list: D001323:Autoantibodies
keywords: 19p; array CGH; hypogammaglobulinemia; subtelomeric microduplication and microdeletion; syndrome with primary immunodeficiency (PID)