TY - JOUR
T1 - Autosomal dominant hypocalcemia due to a truncation in the C-tail of the calcium-sensing receptor
AU - Maruca, Katia
AU - Brambilla, Ilaria
AU - Mingione, Alessandra
AU - Bassi, Lorenzo
AU - Capelli, Silvia
AU - Brasacchio, Caterina
AU - Soldati, Laura
AU - Cisternino, Mariangela
AU - Mora, Stefano
PY - 2017/1/5
Y1 - 2017/1/5
N2 - Autosomal Dominant Hypocalcemia (ADH) is an endocrine disorder due to activating mutations of the calcium-sensing receptor (CASR) gene. We report on a young boy who presented low serum calcium with hypercalciuria, hyperphosphatemia and low serum concentration of parathyroid hormone, not accompanied by classic clinical signs of hypocalcemia. Treatment with calcitriol and calcium did not normalize serum calcium and renal calcium excretion. The use of thiazide diuretics slightly reduced calciuria. Despite high calcium excretion, no signs of nephrocalcinosis were detected. The patient had a prolonged Q-T interval at ECG, which did not normalize during treatment. PCR amplification of CASR coding sequence and direct sequencing of PCR products. showed a novel heterozygous deletion of a cytosine (c.2682delC), responsible for a frameshift (p.S895Pfs*44) and a premature stop codon resulting in a truncation of the CaSR's C-tail. Functional studies indicated increased activity of mutant receptor compared to the wild-type.
AB - Autosomal Dominant Hypocalcemia (ADH) is an endocrine disorder due to activating mutations of the calcium-sensing receptor (CASR) gene. We report on a young boy who presented low serum calcium with hypercalciuria, hyperphosphatemia and low serum concentration of parathyroid hormone, not accompanied by classic clinical signs of hypocalcemia. Treatment with calcitriol and calcium did not normalize serum calcium and renal calcium excretion. The use of thiazide diuretics slightly reduced calciuria. Despite high calcium excretion, no signs of nephrocalcinosis were detected. The patient had a prolonged Q-T interval at ECG, which did not normalize during treatment. PCR amplification of CASR coding sequence and direct sequencing of PCR products. showed a novel heterozygous deletion of a cytosine (c.2682delC), responsible for a frameshift (p.S895Pfs*44) and a premature stop codon resulting in a truncation of the CaSR's C-tail. Functional studies indicated increased activity of mutant receptor compared to the wild-type.
KW - Activating mutation
KW - Autosomal dominant hypocalcemia
KW - Calcium-sensing receptor
KW - Deletion
KW - Mutational analysis
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U2 - 10.1016/j.mce.2016.08.032
DO - 10.1016/j.mce.2016.08.032
M3 - Article
AN - SCOPUS:84994853843
VL - 439
SP - 187
EP - 193
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
SN - 0303-7207
ER -