title: Autosomal-dominant isolated growth hormone deficiency (IGHD type II) with normal GH-1 gene.
abstract: BACKGROUND
  Autosomal-dominant isolated GH deficiency (IGHD) is a rare disorder that is commonly believed to be due to heterozygous mutations in the GH-1 gene (GH-1). These mutations cause the production of a protein that affects the release of the product of the normal allele. Rarely, heterozygous mutations in the gene encoding for HESX-1 gene (HESX-1) may cause autosomal-dominant IGHD, with penetrance that has been shown to be variable in both humans and mice.
  
  
  METHODS
  We have sequenced the whole GH-1 in the index cases of 30 families with autosomal-dominant IGHD. In all the families other possible causes of GH deficiency and other pituitary hormones deficits were excluded. We here describe the clinical, biochemical and radiological picture of the families without GH-1 mutations. In these families, we also sequenced the HESX-1.
  
  
  RESULTS
  The index cases of the five families with autosomal-dominant IGHD had normal GH-1, including the intronic sequences. They had no HESX-1 mutations.
  
  
  CONCLUSIONS
  This study shows that GH-1 mutations are absent in 5/30 (16.6%) of the families with autosomal-dominant IGHD and raises the possibility that mutations in other gene(s) may be involved in IGHD with this mode of transmission.
authors.affiliation: Division of Endocrinology, Department of Medicine and Ilyssa Center for Molecular and Cellular Endocrinology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Danilo
authors.initials: D
authors.lastname: Fintini
authors.forename: Roberto
authors.initials: R
authors.lastname: Salvatori
authors.forename: Souzan
authors.initials: S
authors.lastname: Salemi
authors.forename: Barto
authors.initials: B
authors.lastname: Otten
authors.forename: Graziamaria
authors.initials: G
authors.lastname: Ubertini
authors.forename: Paola
authors.initials: P
authors.lastname: Cambiaso
authors.forename: Primus E
authors.initials: PE
authors.lastname: Mullis
mesh_terms: D000328:Adult; D000368:Aged; D002675:Child, Preschool; D004393:Dwarfism, Pituitary / Q000097:blood / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D019382:Human Growth Hormone / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010375:Pedigree; D010902:Pituitary Gland / Q000033:anatomy & histology; D017422:Sequence Analysis, DNA
chemical_list: D019382:Human Growth Hormone