Clinical characterization of a novel calcium sensing receptor genetic alteration in a Greek patient with autosomal dominant hypocalcemia type 1

OBJECTIVE: Autosomal dominant hypocalcemia (ADH) is a rare familial or sporadic syndrome associated with activating mutations in the calcium sensing receptor ( CaSR ) gene. The aim of this study was to assess the functional significance of a novel CaSR mutation and, moreover, to present the clinical...

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Published in:Hormones (Athens, Greece) Greece), 2017-04, Vol.16 (2), p.200-204
Main Authors: Papadopoulou, Anna, Gole, Evangelia, Melachroinou, Katerina, Trangas, Theoni, Bountouvi, Evaggelia, Papadimitriou, Anastasios
Format: Article
Language:English
Subjects:
Adolescent
Case Report
Endocrinology
Humans
Hypercalciuria - diagnosis
Hypercalciuria - genetics
Hypocalcemia - diagnosis
Hypocalcemia - genetics
Hypoparathyroidism - congenital
Hypoparathyroidism - diagnosis
Hypoparathyroidism - genetics
Male
Medicine
Medicine & Public Health
Metabolic Diseases
Receptors, Calcium-Sensing - genetics
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Summary:OBJECTIVE: Autosomal dominant hypocalcemia (ADH) is a rare familial or sporadic syndrome associated with activating mutations in the calcium sensing receptor ( CaSR ) gene. The aim of this study was to assess the functional significance of a novel CaSR mutation and, moreover, to present the clinical characteristics and the bone mineral density (BMD) progression from early childhood to late puberty in a patient with ADH. DESIGN: Genetic analysis of the CaSR gene was performed in a patient who presented in the neonatal period with hypocalcemic seizures and biochemical features of ADH. The functional impact of the novel mutation identified was assessed in cultured HEK 293T cells, transfected with either the wild type (WT) or mutant CaSR, by evaluating intracellular calcium ([Ca 2+ ] i ) influx after stimulation with extracellular calcium (Ca 2+ ). Several BMD measurements were performed during the patient’s follow-up until late puberty. RESULTS: A novel CaSR mutation (p.L123S) was identified, which, as demonstrated by functional analysis, renders CaSR more sensitive to extracellular changes of Ca 2+ compared with the WT, although the difference is not statistically significant. BMD measurements, from early childhood to late puberty, revealed high normal to elevated BMD. CONCLUSION: We present the first Greek patient, to our knowledge, with sporadic ADH due to a novel gain-of-function mutation of the CaSR gene.
ISSN:1109-3099
2520-8721
DOI:10.14310/horm.2002.1734