title: A novel GH1 mutation in a family with isolated growth hormone deficiency type II.
abstract: BACKGROUND
  Four distinct familial types of isolated GH deficiency (IGHD) have been described so far.
  
  
  OBJECTIVE
  We report a novel nonsense GH1 mutation in a father and a son.
  
  
  METHODS
  Father's height was 137.3 cm (-6.79 SDS); mother's height was 157.3 cm (-1.86 SDS). By the age of 8.25 years, his height was 104.3 cm (-4.82 SDS) and his weight was 18.3 kg (-3.35 SDS). GH stimulation tests had low peak GH value of 6.5 ng/ml (proband) and 6.3 ng/ml (father). Other pituitary hormones and magnetic resonance imaging (MRI) of the pituitary region was normal in both patients. The proband received recombinant human GH (rhGH) treatment (30 μg/kg/day) and he grew 15.4 cm in 15 months.
  
  
  RESULTS
  Sequencing of the GH1 gene revealed a novel heterozygous nonsense mutation in both the father and the son (c.199A>T), which introduces a stop codon in exon 3.
  
  
  CONCLUSIONS
  We present a family with IGHD II, with severe short stature, no phenotypic characteristics of GHD and a novel nonsense mutation in exon 3 of the GH1 gene. As fibroblasts were unavailable, we used computer analysis and we propose a unique mechanism that combines aberrant splicing and derogated GH release from the pituitary with residual secretion of a bioinactive truncated GH peptide.
authors.affiliation: Medical Faculty Skopje, Skopje, Macedonia. gucevz@gmail.com
authors.forename: Zoran
authors.initials: Z
authors.lastname: Gucev
authors.forename: Velibor
authors.initials: V
authors.lastname: Tasic
authors.forename: Liljana
authors.initials: L
authors.lastname: Saranac
authors.forename: Heike
authors.initials: H
authors.lastname: Stobbe
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kratzsch
authors.forename: Jürgen
authors.initials: J
authors.lastname: Klammt
authors.forename: Roland
authors.initials: R
authors.lastname: Pfäffle
mesh_terms: D000328:Adult; D001483:Base Sequence; D018389:Codon, Nonsense; D019382:Human Growth Hormone / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D008297:Male; D012326:RNA Splicing
chemical_list: D018389:Codon, Nonsense; D019382:Human Growth Hormone