title: Growth hormone secretion and immunological function of a male patient with a homozygous STAT5b mutation.
abstract: OBJECTIVE
  STAT5b is a component of the GH signaling pathway. Recently, we described a 31-year-old male patient (height, -5.9 SDS) with a novel homozygous inactivating mutation in the STAT5b gene. The purpose of this study is to describe the phenotype in detail, including GH secretion and immunological function. In addition, we report four family members of this patient, all heterozygous carriers of the mutation.
  
  
  METHODS
  Twenty-four hour GH and prolactin secretion characteristics were assessed by blood sampling at 10-min intervals. An IGF-I generation test was performed. Monocyte function was tested by stimulation of whole blood with lipopolysaccharide (LPS) in the presence or absence of Interferon-gamma (IFN-gamma). In addition, T cell function was determined by measuring proliferative responses of peripheral blood mononuclear cells (PBMC) after stimulation by various polyclonal activators and Interleukin-2 (IL-2). Clinical and biochemical characteristics were determined in the carriers of the mutation.
  
  
  RESULTS
  GH secretory parameters were comparable with that of healthy male controls (mean fat percentage 25), but likely increased in relation to the patient's 40% body fat. The regularity of GH secretion was diminished. Prolactin secretion was increased by sixfold. The IGF-I generation test showed a small increase in IGF-I and IGF-binding protein-3 on lower GH doses and an increase in IGF-I to -2.4 SDS on the highest dose of GH. In vitro, IL-12p40, IL 10, and tumour necrosis factor-alpha (TNF-alpha) production rates by PBMC increased to values within the normal range upon stimulation of LPS. Heterozygous carriers of the mutation did not show abnormalities, although the height of the males was below the normal range.
  
  
  CONCLUSIONS
  This report shows that GH and prolactin secretion were increased in this patient homozygous for a new STAT5b mutation. Although STAT5b plays a role in signaling within immune cells, clinical immunodeficiency is not an obligatory phenomenon of STAT5b deficiency per se. Heterozygous carriers of a STAT5b mutation show no signs of GH insensitivity.
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, The Netherlands. m.j.e.walenkamp@humc.nl.
authors.forename: Marie J E
authors.initials: MJ
authors.lastname: Walenkamp
authors.forename: Solrun
authors.initials: S
authors.lastname: Vidarsdottir
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Pereira
authors.forename: Marcel
authors.initials: M
authors.lastname: Karperien
authors.forename: Jaap
authors.initials: J
authors.lastname: van Doorn
authors.forename: Hermine A
authors.initials: HA
authors.lastname: van Duyvenvoorde
authors.forename: Martijn H
authors.initials: MH
authors.lastname: Breuning
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Roelfsema
authors.forename: M Femke
authors.initials: MF
authors.lastname: Kruithof
authors.forename: Jaap
authors.initials: J
authors.lastname: van Dissel
authors.forename: Riny
authors.initials: R
authors.lastname: Janssen
authors.forename: Jan M
authors.initials: JM
authors.lastname: Wit
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Romijn
mesh_terms: D000293:Adolescent; D001827:Body Height; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D002648:Child; D006720:Homozygote; D019382:Human Growth Hormone / Q000097:blood* / Q000378:metabolism; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010641:Phenotype; D011388:Prolactin / Q000097:blood / Q000378:metabolism; D017471:Receptors, Interferon / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000235:genetics*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000096743:Interferon gamma Receptor
chemical_list: D019382:Human Growth Hormone; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; D007371:Interferon-gamma; D016753:Interleukin-10; D053762:Interleukin-12 Subunit p40; D008070:Lipopolysaccharides; D011388:Prolactin; D017471:Receptors, Interferon; D050799:STAT5 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D000096743:Interferon gamma Receptor; C515497:IGFBP3 protein, human; C494095:STAT5B protein, human