title: Clinical and biochemical characteristics of a male patient with a novel homozygous STAT5b mutation.
abstract: BACKGROUND
  GH insensitivity can be caused by defects in the GH receptor (GHR) or in the postreceptor signaling pathway. Recently, two female patients with severe growth retardation and pulmonary and immunological problems were described with a defect in STAT5b, a critical intermediary of downstream GHR signaling.
  
  
  OBJECTIVE
  The objective was to determine the functional characteristics of a novel STAT5b mutation and describe the phenotype.
  
  
  METHODS
  We describe an adult male patient with short stature [-5.9 sd score (SDS)], delayed puberty, and no history of pulmonary or immunological problems. GH-binding protein level as well as GH secretion characteristics were normal. Plasma prolactin level was elevated. Extremely low levels of IGF-I (-6.9 SDS), IGF-binding protein-3 (-12 SDS), and acid-labile subunit (-7.5 SDS) were found.
  
  
  RESULTS
  We found a homozygous frameshift mutation in the STAT5b gene (nucleotide 1102-3insC, Q368fsX376), resulting in an inactive truncated protein, lacking most of the DNA binding domain and the SH2-domain.
  
  
  CONCLUSIONS
  This report confirms the essential role of STAT5b in GH signaling in the human. We show for the first time that immunological or pulmonary problems or elevated GH secretion are not obligatory signs of STAT5b deficiency, whereas hyperprolactinemia appears to be part of the syndrome. Therefore, in patients with severe short stature, signs of GH insensitivity, and a normal GHR, analysis of the STAT5b gene is recommended.
authors.affiliation: Department of Pediatrics J6-S, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: Solrun
authors.initials: S
authors.lastname: Vidarsdottir
authors.forename: Marie J E
authors.initials: MJ
authors.lastname: Walenkamp
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: Stefan
authors.initials: S
authors.lastname: White
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: D000328:Adult; D001483:Base Sequence; D002352:Carrier Proteins / Q000097:blood; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D016368:Frameshift Mutation; D006023:Glycoproteins / Q000097:blood; D006130:Growth Disorders / Q000097:blood / Q000235:genetics*; D019382:Human Growth Hormone / Q000502:physiology; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D050799:STAT5 Transcription Factor / Q000235:genetics*; D017422:Sequence Analysis, DNA; D015398:Signal Transduction
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; D018972:Insulin-Like Growth Factor Binding Protein 3; D050799:STAT5 Transcription Factor; C494095:STAT5B protein, human; C075944:insulin-like growth factor binding protein, acid labile subunit; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D004247:DNA