title: A new heterozygous mutation (D196N) in the Gs alpha gene as a cause for pseudohypoparathyroidism type IA in a boy who had gallstones.
abstract: BACKGROUND
  Pseudohypoparathyroidism (PHP) is characterized by hypocalcemia and hyperphosphatemia in association with an increased secretion of parathyroid hormone (PTH) due to decreased target tissue responsiveness to PTH. Patients with PHP type Ia are not only resistant to PTH, but also to other hormones that bind to receptors coupled to stimulatory G protein (Gsalpha). PHP Ia and Albright hereditary osteodystrophy (AHO) are caused by a reduced activity of the Gsalpha protein. Heterozygous inactivating Gs alpha (GNAS) gene mutations have been identified in these patients.
  
  
  METHODS
  We studied a boy with PHP Ia. During follow-up the patient developed elevated liver enzyme serum levels and abdominal discomfort. Gsalpha activity was measured in erythrocyte membranes from the patient and the GNAS coding region of Gsalpha sequenced.
  
  
  RESULTS
  Gsalpha activity was reduced (62%) and molecular analysis revealed a new heterozygous GNAS gene mutation (D196N). Gallstones were diagnosed and cholecystectomy was performed. Biochemical analysis revealed cholesterol stones, a condition that was not reported before in PHP Ia.
  
  
  CONCLUSIONS
  Cholesterol gallstones may rarely be associated with PHP Ia and should be taken into account.
authors.affiliation: Children's Hospital of the Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Winter
authors.forename: Olaf
authors.initials: O
authors.lastname: Hiort
authors.forename: Pia
authors.initials: P
authors.lastname: Hermanns
authors.forename: Susanne
authors.initials: S
authors.lastname: Thiele
authors.forename: Joachim
authors.initials: J
authors.lastname: Pohlenz
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D002648:Child; D002784:Cholesterol / Q000032:analysis; D002864:Chromogranins; D017124:Conserved Sequence; D004247:DNA / Q000235:genetics; D004912:Erythrocytes / Q000378:metabolism; D005091:Exons; D005532:Foot Deformities, Congenital / Q000235:genetics; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000097:blood / Q000235:genetics*; D042882:Gallstones / Q000737:chemistry / Q000150:complications* / Q000235:genetics*; D006228:Hand Deformities, Congenital / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D011547:Pseudohypoparathyroidism / Q000145:classification / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D017386:Sequence Homology, Amino Acid
chemical_list: D002864:Chromogranins; D004247:DNA; D002784:Cholesterol; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs