[Disorders Caused by Mutations in Calcium-Sensing Receptor and Related Diseases.]
Sensing of extracellular calcium(Ca2+)levels involves the Ca-sensing receptor(CaSR), its downstream signaling molecule Gα11, and the adaptor-related protein complex 2(AP2)that plays a role in clathrin-dependent endocytosis of CaSR. Inactivating mutations in CaSR cause familial hypocalciuric hypercalcemia type 1(FHH1)and neonatal severe hyperparathyroidism(NSHPT), while activating mutations lead to autosomal dominant hypocalcemia type 1(ADH1)and Bartter syndrome type Ⅴ. Recent studies have identified that inactivating mutations in Gα11 and σ-subunit of AP2(AP2σ)also cause FHH, and these conditions have been classified as FHH2 and FHH3, respectively. In addition, it has been revealed that activating mutations in Gα11 are responsible for ADH(ADH2). Calcimimetics and calcilytics may be beneficial in the treatment of these disorders.
Disorders Caused by Mutations in Calcium-Sensing Receptor and Related Diseases.
Toshimi
T
Michigami
D002118:Calcium / Q000378:metabolism; D002128:Calcium Metabolism Disorders / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling; D006801:Humans; D009154:Mutation; D021381:Protein Transport; D044169:Receptors, Calcium-Sensing / Q000235:genetics / Q000378:metabolism*
D044169:Receptors, Calcium-Sensing; D002118:Calcium