title: A novel frame shift mutation in the GHRH receptor gene in familial isolated GH deficiency: early occurrence of anterior pituitary hypoplasia.
abstract: BACKGROUND
  Mutations in the genes encoding for GHRH receptor (GHRHR) and GH (GH1) are the most common cause of familial isolated GH deficiency (IGHD). GHRHR mutations are often associated with anterior pituitary hypoplasia (APH), but this has been reported almost exclusively in children older than 8 yr. We analyzed the GHRHR and measured pituitary size in a consanguineous family with the father and three of the five siblings with IGHD.
  
  
  OBJECTIVE
  The aim of the study was to find the mutated gene in a family with severe IGHD.
  
  
  METHODS
  We sequenced the whole GHRHR coding regions and the intron-exon boundaries from peripheral DNA of the index patient. After identifying the novel mutation, we sequenced the region of interest in the other members of the family. We measured the anterior pituitary volume from magnetic resonance imaging (MRI).
  
  
  RESULTS
  The father and the three affected children were homozygous for a new frame-shift mutation in the coding sequence of exon 4 (corresponding to the extracellular domain of the receptor) (c.340delG) that places the downstream sequence out of frame [corrected]. The mother and two unaffected siblings were heterozygous for the mutation. Two of the affected children had MRI evidence of APH before reaching 6 yr of age.
  
  
  CONCLUSIONS
  We describe a new mutation in the GHRHR in a family with IGHD. The presence of frank APH before age 6 yr shows that MRI-evident reduced pituitary size can be present in GHRHR mutations even in children younger than 8 yr of age.
authors.affiliation: Department of Medicine, Division of Endocrinology, Johns Hopkins University, Baltimore, Maryland 21287, USA. salvator@jhmi.edu
authors.forename: Rugia
authors.initials: R
authors.lastname: Shohreh
authors.forename: Rosa
authors.initials: R
authors.lastname: Sherafat-Kazemzadeh
authors.forename: Youn Hee
authors.initials: YH
authors.lastname: Jee
authors.forename: Ari
authors.initials: A
authors.lastname: Blitz
authors.forename: Roberto
authors.initials: R
authors.lastname: Salvatori
mesh_terms: D000293:Adolescent; D001827:Body Height / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics* / Q000502:physiology*; D006130:Growth Disorders / Q000209:etiology; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use; D006801:Humans; D007438:Introns / Q000235:genetics; D008279:Magnetic Resonance Imaging; D010375:Pedigree; D010900:Pituitary Diseases / Q000473:pathology*; D010903:Pituitary Gland, Anterior / Q000473:pathology*; D018013:Receptors, Neuropeptide / Q000235:genetics* / Q000502:physiology*; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000235:genetics* / Q000502:physiology*; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D004247:DNA; C048250:somatotropin releasing hormone receptor