title: Growth hormone insensitivity and severe short stature in siblings: a novel mutation at the exon 13-intron 13 junction of the STAT5b gene.
abstract: OBJECTIVE
  Growth hormone insensitivity (GHI) is characterized by severe short stature, high serum growth hormone (GH), low serum IGF-I and IGFBP-3 levels and is classically associated with genetic defects of the GH receptor (GHR). Recently, mutations of the STAT5b gene have been identified and shown to be associated with GHI and severe IGF deficiency. We investigated 2 sisters from a consanguineous family from Kuwait, with clinical and biochemical features of GHI, in whom no molecular defects in the GHR were identified.
  
  
  METHODS
  Serum and DNA were analyzed.
  
  
  RESULTS
  In addition to GHI, siblings 2 and 1 presented with, respectively, a diagnosis of juvenile idiopathic arthritis and recurrent pulmonary infections. Molecular analysis of the STAT5b gene revealed a novel homozygous deletion of a G at the junction of exon 13-intron 13. The parents, who are of normal height, were heterozygous for the mutation.
  
  
  CONCLUSIONS
  This is the first STAT5b defect to be identified in siblings, further supporting the autosomal recessive mode of transmission of STAT5b deficiency. The results affirm that defective STAT5b is an etiology for IGF deficiency and the GHI phenotype, and emphasize the importance of considering this diagnosis in patients with IGF deficiency, especially when associated with diverse immunological problems.
authors: Department of Pediatrics, Oregon Health and Sciences University, Portland, OR 97239-3098, USA.
authors: Vivian
authors: V
authors: Hwa
authors: Cecilia
authors: C
authors: Camacho-Hübner
authors: Brian M
authors: BM
authors: Little
authors: Alessia
authors: A
authors: David
authors: Lou A
authors: LA
authors: Metherell
authors: Nesrin
authors: N
authors: El-Khatib
authors: Martin O
authors: MO
authors: Savage
authors: Ron G
authors: RG
authors: Rosenfeld
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001827:Body Height / Q000235:genetics*; D019556:COS Cells; D002675:Child, Preschool; D002522:Chlorocebus aethiops; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006801:Humans; D007438:Introns; D046150:Laron Syndrome / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D050799:STAT5 Transcription Factor / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D035781:Siblings; D014162:Transfection
chemical_list: D050799:STAT5 Transcription Factor; C494095:STAT5B protein, human