Rare diseases caused by abnormal calcium sensing and signalling

Area of Science:

• Endocrinology
• Molecular Biology
• Genetics

Background:

• The calcium-sensing receptor (CaSR) is a G-protein-coupled receptor essential for detecting extracellular calcium levels.
• CaSR plays a critical role in maintaining calcium homeostasis.
• Defects in the CaSR gene are linked to various diseases involving altered serum calcium concentrations.

Purpose of the Study:

• To summarize the role of the calcium-sensing receptor (CaSR) in calcium homeostasis.
• To describe the clinical implications of CaSR gene mutations.
• To explore the association between CaSR gene polymorphisms and malignancy risk.

Main Methods:

• Review of existing literature on CaSR function and genetics.
• Analysis of the impact of CaSR gene mutations on calcium metabolism.
• Examination of studies investigating CaSR polymorphisms and disease associations.

Main Results:

• Activating CaSR mutations lead to increased calcium sensitivity, causing autosomal dominant hypocalcemia or Bartter syndrome type V.
• Inactivating CaSR mutations result in calcium resistance, leading to familial hypocalciuric hypercalcemia (FHH1) or neonatal severe hyperparathyroidism (NSHPT).
• Mutations in genes of CaSR partner proteins are linked to FHH2 and FHH3. Common CaSR polymorphisms may increase malignancy risk but do not typically affect calcium homeostasis.

Conclusions:

• CaSR is a key regulator of calcium homeostasis, and its genetic variations have significant clinical consequences.
• CaSR gene mutations are directly implicated in hypocalcemic and hypercalcemic disorders.
• Further research into CaSR polymorphisms may reveal links to cancer susceptibility.