title: Autosomal dominant hypocalcemia due to a truncation in the C-tail of the calcium-sensing receptor.
abstract: 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.
authors: Laboratory of Pediatric Endocrinology, IRCCS San Raffaele Scientific Institute, via Olgettina 60, 20132, Milan, Italy.
authors: Katia
authors: K
authors: Maruca
authors: Department of Pediatrics, IRCCS Policlinico San Matteo, University of Pavia, viale C. Golgi 19, 27100, Pavia, Italy.
authors: Ilaria
authors: I
authors: Brambilla
authors: Department of Health Sciences, Università degli Studi di Milano, via A. di Rudinì 8, 20124, Milan, Italy.
authors: Alessandra
authors: A
authors: Mingione
authors: Department of Pediatrics, IRCCS Policlinico San Matteo, University of Pavia, viale C. Golgi 19, 27100, Pavia, Italy.
authors: Lorenzo
authors: L
authors: Bassi
authors: Laboratory of Pediatric Endocrinology, IRCCS San Raffaele Scientific Institute, via Olgettina 60, 20132, Milan, Italy.
authors: Silvia
authors: S
authors: Capelli
authors: Department of Health Sciences, Università degli Studi di Milano, via A. di Rudinì 8, 20124, Milan, Italy.
authors: Caterina
authors: C
authors: Brasacchio
authors: Department of Health Sciences, Università degli Studi di Milano, via A. di Rudinì 8, 20124, Milan, Italy.
authors: Laura
authors: L
authors: Soldati
authors: Department of Pediatrics, IRCCS Policlinico San Matteo, University of Pavia, viale C. Golgi 19, 27100, Pavia, Italy.
authors: Mariangela
authors: M
authors: Cisternino
authors: Laboratory of Pediatric Endocrinology, IRCCS San Raffaele Scientific Institute, via Olgettina 60, 20132, Milan, Italy. Electronic address: mora.stefano@hsr.it.
authors: Stefano
authors: S
authors: Mora
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D002648:Child; D005799:Genes, Dominant; D057809:HEK293 Cells; D006801:Humans; D053565:Hypercalciuria / Q000235:genetics*; D006996:Hypocalcemia / Q000235:genetics*; D007011:Hypoparathyroidism / Q000151:congenital* / Q000235:genetics; D007231:Infant, Newborn; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation; D044169:Receptors, Calcium-Sensing / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D044169:Receptors, Calcium-Sensing; D048052:Mitogen-Activated Protein Kinase 3
keywords: Activating mutation; Autosomal dominant hypocalcemia; Calcium-sensing receptor; Deletion; Mutational analysis