title: New mutation type in pseudohypoparathyroidism type Ia.
abstract: BACKGROUND
  The GNAS gene encodes the alpha-subunit of the stimulatory G proteins, which play a crucial role in intracellular signal transduction of peptide and neurotransmitter receptors. Heterozygous inactivating maternally inherited mutations of GNAS (including translation initiation mutations, amino acid substitutions, nonsense mutations, splice site mutations and small insertions or deletions) lead to a phenotype in which Albright hereditary osteodystrophy is associated with pseudohypoparathyroidism type Ia.
  
  
  OBJECTIVE
  We sought to identify the molecular defect in a patient who was thought to have PHP-Ia.
  
  
  RESULTS
  The GNAS gene of a 5-year-old boy with brachydactily, mental retardation, pseudohypoparathyroidism and congenital hypothyroidism was investigated. We found a heterozygous inversion of exon 2 and part of intron 1 of de novo origin. Molecular studies of cDNA from blood RNA demonstrated that both the normal and the mutant variants were stable and that new splice-sites were generated.
  
  
  CONCLUSIONS
  This report demonstrates the first evidence for an inversion at the GNAS gene responsible of pseudohypoparathyroidism type Ia.
authors.affiliation: Endocrinology and Diabetes Research Group, Hospital de Cruces, Barakaldo, Basque Country, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Fernandez-Rebollo
authors.forename: Raquel
authors.initials: R
authors.lastname: Barrio
authors.forename: Gustavo
authors.initials: G
authors.lastname: Pérez-Nanclares
authors.forename: Atilano
authors.initials: A
authors.lastname: Carcavilla
authors.forename: Intza
authors.initials: I
authors.lastname: Garin
authors.forename: Luis
authors.initials: L
authors.lastname: Castaño
authors.forename: Guiomar Pérez
authors.initials: GP
authors.lastname: de Nanclares
mesh_terms: D001483:Base Sequence; D002675:Child, Preschool; D002864:Chromogranins; D003409:Congenital Hypothyroidism / Q000150:complications / Q000235:genetics; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000150:complications / Q000235:genetics; D008297:Male; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology; D009690:Nucleic Acid Conformation; D010375:Pedigree; D017689:Polydactyly / Q000150:complications / Q000235:genetics; D011547:Pseudohypoparathyroidism / Q000151:congenital / Q000235:genetics*
chemical_list: D002864:Chromogranins; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs