New mutation in the CASR gene in a family with familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT)

Abstract

A loss of calcium-sensing receptor (CASR) function due to inactivating mutations can cause familial hypocalciuric hypercalcemia (FHH) or neonatal severe hyperparathyroidism (NSHPT). NSHPT represents the most severe expression of FHH and courses as a life-threatening condition. The aim of this study was to identify and characterize a CASR mutation in a female infant brought to the health service due to dehydration, apathy, lack of breast feeding and severe hypercalcemia. Molecular analysis was performed on genomic DNA of the index case and her parents. A novel homozygous mutation (p.E519X) in CASR was identified in the proband; both mother and father had the same mutation in heterozygous state, confirming their FHH condition. The mutation results in a truncated and inactive protein due to the lack of transmembrane and intracellular domains. The identification of this novel CASR gene mutation established the basis of hypercalcemia in this family and allowed a genetic counseling.

Parathyroid Function and Disease during Pregnancy, Lactation, and Fetal/Neonatal Development

“…In some reported cases the diagnosis has been delayed for over a month after birth. 258 The parathyroids are grossly enlarged and serum PTH is quite high. This is usually a fatal condition unless parathyroidectomy is urgently performed, 250 although rarer cases have spontaneously resolved into milder hypercalcemia without surgery.…”

Engendering biased signalling from the calcium‐sensing receptor for the pharmacotherapy of diverse disorders

“…Ma et al ., ) or nonsense mutations that introduce premature stop codons and thereby truncate the receptor protein (e.g. Rodrigues et al ., ; Ward et al ., ) also induce loss of function and/or expression. Receptor truncation can also arise from mutations in acceptor splice sites (D'Souza‐Li et al ., ) or from the insertion of Alu elements (Janicic et al ., ).…”

Prostate Cancer Metastatic to Bone has Higher Expression of the Calcium-Sensing Receptor (CaSR) than Primary Prostate Cancer

“…Naturally occurring mutations cause familial hypocalciuric hypercalcemia (FHH) [1] , neonatal severe hyperparathyroidism (NSHPT) [2] and autosomal dominant hypocalcemia with hypercalciuria (ADHH) [3] . The CaSR was first cloned from bovine parathyroid glands [4] and belongs to class C of the G protein-coupled receptors (GPCR).…”