A novel mutation of the calcium-sensing receptor gene in a Greek family from Nisyros.

PURPOSE

Inactivating mutations of the calcium-sensing receptor (CASR) gene cause familial hypocalciuric hypercalcaemia (FHH). Here we report three siblings with FHH caused by a novel mutation in the CASR.

METHODS

The case subject was a 60-year-old patient referred because of mild hypercalcaemia, increased PTH levels and persistently low calcium/creatinine ratio. FHH was suspected and a family biochemical and genetic analysis was performed.

RESULTS

Sequencing of the CASR gene revealed a frameshift mutation (Val258Arg) in the extracellular domain of the CASR that creates a premature 46 amino acids stop codon which leads to a truncated protein that might affect its function. This heterozygous loss-of-function mutation in the CaSR gene causes reduced CaSR sensing ability resulting in the clinical manifestation of FHH.

CONCLUSION

We hereby report the identification of a novel heterozygous loss-of-function mutation of the CASR gene in a Greek family from Nisyros island. Functional studies are needed to clarify the exact role of this mutation in CASR activity.