title: A novel growth hormone receptor gene deletion mutation in a patient with primary growth hormone insensitivity syndrome (Laron syndrome).
abstract: OBJECTIVE
  Growth hormone (GH) insensitivity syndrome (Laron syndrome) is known to be caused by genetic disorders of the GH-IGF-1 axis. Although many mutations in the GH receptor have been identified, there have been only a few reports of deletions of the GH receptor gene.
  
  
  METHODS
  A Japanese adult female patient with Laron syndrome was subjected to chromosome analysis with basic G-banding and also with a high accuracy technique. Each exon of the GH receptor gene was amplified by means of PCR. Since this patient was diagnosed with osteoporosis, the effects of alendronate on bone mineral density (BMD) were also examined.
  
  
  RESULTS
  The chromosome analysis with the high accuracy technique demonstrated a large deletion of the short arm in one allele of chromosome 5 from p11 to p13.1 [46, XX, del (5) (p11-p13.1)]. PCR amplification of exons of the GH receptor gene showed that only exons 2 and 3 were amplified. Low-dose IGF-1 administration (30microg/kg body weight) failed to increase her BMD, whereas alendronate administration resulted in an increase associated with a decrease in urinary deoxypyridinoline (DPD) and serum osteocalcin concentrations.
  
  
  CONCLUSIONS
  The GH receptor gene of the patient was shown to lack exons 4-10. To the best of our knowledge, this is the third case report of Laron syndrome with large GH receptor deletion. Alendronate was effective for the enhancement of BMD.
authors.affiliation: Department of Molecular Medicine, Osaka University Graduate School of Medicine (C-4), 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Kouhara
authors.forename: Keiji
authors.initials: K
authors.lastname: Iida
authors.forename: Kazuo
authors.initials: K
authors.lastname: Chihara
authors.forename: Soji
authors.initials: S
authors.lastname: Kasayama
mesh_terms: D015519:Bone Density; D002478:Cells, Cultured; D020732:Cytogenetic Analysis; D004252:DNA Mutational Analysis; D005260:Female; D017353:Gene Deletion; D006801:Humans; D046150:Laron Syndrome / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D011986:Receptors, Somatotropin / Q000235:genetics*
chemical_list: D011986:Receptors, Somatotropin