Analysis of AP2S1, a calcium-sensing receptor regulator, in familial and sporadic isolated hypoparathyroidism

J Clin Endocrinol Metab. 2014 Mar;99(3):E469-73. doi: 10.1210/jc.2013-3136. Epub 2014 Jan 1.


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.

Aim: 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.

Results and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Protein Complex 2 / genetics*
  • Adaptor Protein Complex sigma Subunits / genetics*
  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Cohort Studies
  • DNA Mutational Analysis
  • Family
  • Female
  • Humans
  • Hypoparathyroidism / genetics*
  • Hypoparathyroidism / metabolism
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Pedigree
  • Receptors, Calcium-Sensing / metabolism*
  • Young Adult


  • AP2S1 protein, human
  • Adaptor Protein Complex 2
  • Adaptor Protein Complex sigma Subunits
  • Receptors, Calcium-Sensing