title: Analysis of AP2S1, a calcium-sensing receptor regulator, in familial and sporadic isolated hypoparathyroidism.
abstract: BACKGROUND
  Except after neck surgery, hypoparathyroidism is a rare disease caused by defects in genes involved in parathyroid gland development (TBX1/22q11.2 del, GCMB, GATA3, TBCE) or function [calcium sensing receptor (CASR), GNA11, PTH], or the autoimmune polyglandular syndrome type 1 (AIRE). Approximately 90% of sporadic cases and 30% of familial cases of isolated hypoparathyroidism remain unexplained. Recurrent missense mutations in AP2S1, a calcium-sensing receptor regulator, have been recently identified in familial hyperparathyroidism.
  
  
  OBJECTIVE
  The aim of the study was to investigate AP2S1 as a putative hypoparathyroidism-causing gene.
  
  
  METHODS
  Sequencing analysis and quantitative genomic PCR of the AP2S1 gene in a large cohort of 10 index cases (from nine families) and 50 sporadic cases affected with isolated hypoparathyroidism were investigated.
  
  
  CONCLUSIONS
  None of the 60 patients presented with nucleotidic changes or copy number variation in the AP2S1 gene, thereby excluding AP2S1 defects as a frequent cause of isolated hypoparathyroidism.
authors.affiliation: INSERM Unité 986 (A.-S.L., V.G., C.S., A.Lin.), Hôpital Bicêtre-Paris-Sud; Assistance Publique-Hôpitaux de Paris, Service d'Endocrinologie et Diabétologie de l'Enfant (L.E., A.Lin.), Hôpital Bicêtre-Paris-Sud Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore (L.E., C.S., A.Lin.); and Faculté de Médecine ( (B.F., J.B., A.G.-M., A.Lin.) and INSERM Unité Mixte de Recherche en Santé 693 (B.F., J.B., A.G.-M.), Université Paris Sud, 94270 Le Kremlin Bicêtre, France; Service de Pédiatrie (A.-S.L., A.Lie.) and Service de Génétique et Cytogénétique (C.M.), Centre Hospitalier Universitaire Limoges, 87000 Limoges, France; Service de Génétique Moléculaire (G.B., C.S.), Centre Hospitalier Universitaire Bichat, 75870 Paris, France; Service de Génétique Moléculaire, Pharmacogénétique, et Hormonologie (B.F., J.B., A.G.-M.), Hôpital Bicêtre-Paris-Sud, Assistance Publique-Hôpitaux de Paris, 94270 Paris, France; Service d'Endocrinologie et Métabolisme (S.H.), Centre Hospitalier Universitaire Nice, 06000 Nice, France; Service de Médecine Interne (D.V.), Centre Hospitalier Louis Mourier, 92700 Colombes, France; and Service de Pédiatrie (S.S.), Centre Hospitalier Universitaire Strasbourg, 67085 Strasbourg, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Lambert
authors.forename: Virginie
authors.initials: V
authors.lastname: Grybek
authors.forename: Bruno
authors.initials: B
authors.lastname: Francou
authors.forename: Laure
authors.initials: L
authors.lastname: Esterle
authors.forename: Guylène
authors.initials: G
authors.lastname: Bertrand
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bouligand
authors.forename: Anne
authors.initials: A
authors.lastname: Guiochon-Mantel
authors.forename: Sylvie
authors.initials: S
authors.lastname: Hieronimus
authors.forename: Dorit
authors.initials: D
authors.lastname: Voitel
authors.forename: Sylvie
authors.initials: S
authors.lastname: Soskin
authors.forename: Corinne
authors.initials: C
authors.lastname: Magdelaine
authors.forename: Anne
authors.initials: A
authors.lastname: Lienhardt
authors.forename: Caroline
authors.initials: C
authors.lastname: Silve
authors.forename: Agnès
authors.initials: A
authors.lastname: Linglart
mesh_terms: D033962:Adaptor Protein Complex 2 / Q000235:genetics*; D034002:Adaptor Protein Complex sigma Subunits / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D006801:Humans; D007011:Hypoparathyroidism / Q000235:genetics* / Q000378:metabolism; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D044169:Receptors, Calcium-Sensing / Q000378:metabolism*; D055815:Young Adult
chemical_list: C510065:AP2S1 protein, human; D033962:Adaptor Protein Complex 2; D034002:Adaptor Protein Complex sigma Subunits; D044169:Receptors, Calcium-Sensing