Abstract
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.
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References
Thakker V, 2004 Diseases associated with the extracellular calcium-sensing receptor. Cell Calcium 35: 275–282.
Bilezikian P, Potts T, Fuleihan H, et al, 2002 Summary statement from a workshop on asymptomatic primary hyperparathyroidism: a perspective for the 21st century. J Clin Endocrinol Metab 87: 5353–5361.
Hendy N, Guarnieri V, Canaff L, 2009 Calcium-sensing receptor and associated diseases. Prog Mol Biol Transl Sci 89: 31–95.
Yun H, Wong Y, Chase M, et al, 2007 Genetic variation at the calcium-sensing receptor (CASR) locus: implications for clinical molecular diagnostics. Clin Biochem 40: 551–561.
D’Souza-Li L, Yang B, Canaff L, et al, 2002 Identification and functional characterization of novel calcium-sensing receptor mutations in familial hypocalciuric hypercalcaemia and autosomal dominant hypocalcaemia. J Clin Endocrinol Metab 87: 1309–1318.
Brown M, 2000 Familial hypocalciuric hypercalcemia and other disorders with resistance to extracellular calcium. Endocrinol Metab Clin North Am 29: 503–522.
Khosla S, Ebeling R, Firek F, Burritt M, Kao C, Heath H, 1993 Calcium infusion suggests a “set-point” abnormality of parathyroid gland function in familial benign hypercalcemia and more complex disturbances in primary hyperparathyroidism. J Clin Endocrinol Metab 76: 715–720.
Varghese J, Rich T, Jimenez C, 2011 Benign Familial Hypocalciuric Hypercalcemia. Endocr Pract 17: 13–17.
Shinall C, McCrystal Dahir K, Broome T, 2014 Differentiating Familial Hypocalciuric Hypercalcemia from Primary Hyperparathyroidism. Endocr Pract 19: 697–702.
Pidasheva S, D’Souza-Li L, Canaff L, Cole E, Hendy N, 2004 CASRdb:calcium-sensing receptor locus-specific database for mutations causing familial (benign) hypocalciuric hypercalcemia. Hum Mutat 24: 107–111.
Kristiansen H, Rødbro P, Christiansen C, Brøchner J, Carl J, 1985 Familial hypocalciuric hypercalsaemia II in testinal calcium absorption and vitamin D metabolism. Clin Endocrinol 23: 511–517.
D’Souza-Li L, Canaff L, Janicic N, Cole E, Hendy N, 2001 An acceptor splice site mutation in the calcium-sensing receptor (CASR) gene in familial hypocalciuric hypercalcaemia and neonatal severe hyperparathyroidism. Hum Mutat 18: 411–421.
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Zapanti, E., Polonifi, A., Kokkinos, M. et al. A novel mutation of the calcium-sensing receptor gene in a Greek family from Nisyros. Hormones 14, 321–325 (2015). https://doi.org/10.14310/horm.2002.1586
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DOI: https://doi.org/10.14310/horm.2002.1586