title: Extreme elevation of serum growth hormone-binding protein concentrations resulting from a novel heterozygous splice site mutation of the growth hormone receptor gene.
abstract: OBJECTIVE
  Circulating growth hormone-binding protein (GHBP), in humans, is the proteolytic product of the growth hormone receptor (GHR). We investigated a prepubertal male subject who was of short stature, but who had a markedly elevated serum level of GHBP.
  
  
  METHODS
  Serum and DNA from the patient and his mother were analyzed.
  
  
  RESULTS
  Both the patient and mother had serum GHBP concentrations over 100-fold higher than normal, by assays, and Western and ligand blot analysis. Sequencing of the GHR gene revealed a novel heterozygous C>A transversion at position 785-3 in the acceptor splice site of intron 7.
  
  
  CONCLUSIONS
  In silico analysis of the altered sequence suggested that 785-3(C>A) is a splicing mutation, with either retention of intron 7 or the skipping of exon 8. The consequence is a truncated GHR lacking the transmembrane domain (encoded by exon 8) and the cytoplasmic domain. We hypothesize that this GHR variant cannot anchor to the cell membrane, and the continual secretion into the circulation explains the elevated levels of serum GHBP detected in the patient and his mother. Despite this mutation, the presence of the wild-type GHR allele, presumably, permits some normality in GH-induced action.
authors.affiliation: Department of Pediatrics, Oregon Health & Science University, Portland, OR 97239-3098, USA.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Aalbers
authors.forename: Daisy
authors.initials: D
authors.lastname: Chin
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Pratt
authors.forename: Brian M
authors.initials: BM
authors.lastname: Little
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Frank
authors.forename: Vivian
authors.initials: V
authors.lastname: Hwa
authors.forename: Ron G
authors.initials: RG
authors.lastname: Rosenfeld