TABLE 2

Calcitropic disorders caused by germline CASR, GNA11, and AP2S1 mutations

Gene Mutation and DiseaseGenotypeSerum CalciumSerum PTHUrine Calcium
CASR mutations
Loss-of-function
 FHH1HeterozygousaHighNormal or highLow
 NSHPTHeterozygous, compound heterozygous, or homozygousHighHighNormal, low or high
 Primary hyperparathyroidism (PHPT)bHeterozygous or homozygousHighHighNormal, low or high
Gain-of-function
 ADH1HeterozygousaLowNormal or lowNormal, low or high
 Bartter syndrome type VHeterozygousLowLowHigh
GNA11 mutations
Loss-of-function
 FHH2HeterozygousHighNormal or highNormal or low
Gain-of-function
 ADH2HeterozygousLowNormal or lowNormal or low
AP2S1 mutations
Loss-of-function
 FHH3HeterozygousHighNormal or highLow
  • a May occasionally be caused by homozygous CASR mutations (Lietman et al., 2009; Cavaco et al., 2018).

  • b CASR mutations are a rare cause of primary hyperparathyroidism.