GNA11 Variants Identified in Patients with Hypercalcemia or Hypocalcemia
Authors' conclusion
Thus, this study identified likely disease-causing GNA11 variants in <1% of probands with hypercalcemia or hypocalcemia and highlights the occurrence of GNA11 rare variants that are benign polymorphisms.
Study context
- Population
- Probands referred for investigation of genetic causes for hypercalcemia or hypocalcemia
- Participants
- >1,200 probands
- Outcome
- Germline GNA11 variants
Methodological details10-year period, in silico analysis, 3D homology modelling, in vitro functional studies
- 10-year period
- In silico analysis
- 3D homology modelling
- In vitro functional studies
Main finding
As reported in the abstract
- Different germline GNA11 variants identified
- 37
- Synonymous variants
- 14
- Noncoding variants
- 12
- Nonsynonymous variants
- 11
- Nonsynonymous variants reported as FHH2- or ADH2-causing (Thr54Met, Arg60His, Arg60Leu, Gly66Ser, Arg149His, Arg181Gln, Phe220Ser, Val340Met, Phe341Leu)
- 9
- Probands with these reported disease-causing variants
- 13
- Probands with likely disease-causing GNA11 variants
- <1%
Further findings
Synonymous and noncoding variants
- Predicted benign or likely benign by in silico analysis; synonymous variants in both hypercalcemic and hypocalcemic individuals
- 5
- Noncoding variants in both hypercalcemic and hypocalcemic individuals
- 3
Met87Val variant
- Identified in a hypercalcemic individual; predicted uncertain significance; homology modelling suggested likely benign; no differences in intracellular calcium responses vs wild-type Met87 in calcium-sensing receptor (CaSR)-expressing HEK293 cells, consistent with benign polymorphism
- Ala65Thr predicted benign
40bp-5'UTR deletion and 15bp-intronic deletion (hypercalcemic individuals only)
- Decreased luciferase expression in vitro but no alterations in GNA11 mRNA or Gα11 protein levels and no splicing abnormality, respectively; confirmed benign polymorphisms
Original publication
GNA11 Variants Identified in Patients with Hypercalcemia or Hypocalcemia. J Bone Miner Res. Published 27 March 2023. doi:10.
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