Identification of a novel mutation disrupting the DNA binding activity of GCM2 in autosomal recessive familial isolated hypoparathyroidism

Abstract

Heterozygous defects in the calcium sensing receptor (CASR) have been detected in autosomal dominant FIH and sporadic cases of hypoparathyroidism.6–8 All known CASR mutations in FIH lead to receptor activation.9,10 The CASR normally functions to provide a negative feedback loop, whereby binding of extracellular Ca2+ activates the receptor, resulting in decreased PTH secretion by parathyroid cells, but also through inhibition of calcium reabsorption in the renal distal tubule. Constitutive activation of this receptor therefore results in hypocalcaemia and hypercalciuria.