ECE2018 Guided Posters Parathyroid (12 abstracts)
A novel mutation in the calcium sensing receptor GENE IN AN Italian family affected by autosomal dominant hypocalcemia
Laura Mazoni 1 , Simona Borsari 2 , Elena Pardi 2 , Federica Saponaro 1 , Chiara Banti 2 , Giulia Marconcini 2 , Claudio Marcocci 2 & Filomena Cetani 3
1Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; 2Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; 3Universital Hospital of Pisa, Endocrine Unit 2, Pisa, Italy.
The G protein-coupled calcium sensing receptor (CaSR), widely expressed on the surface of parathyroid chief cells and in the kidney, plays a central role in calcium homeostasis. Activating mutations of CaSR gene are responsible for autosomal dominant hypocalcemia (ADH), a rare disorder caused by hypocalcemia, hyperphosphatemia, hypercalciuria and inadequately low concentration of parathyroid hormone (PTH). In this study, we report a family affected by ADH. The proband, a 26 year-old Italian woman, was referred to our Department in 2011 for a mild asymptomatic hypocalcemia detected in 2009 during routine blood tests. Biochemical evaluation confirmed a mild hypocalcemia (mean value: 8±0.26 mg/dl, normal range: 8.6–10.2), normal serum PTH (mean value 22±5.57 pg/ml, normal range 8–40) and relative 24 h urinary calcium excretion (mean value: 171±30.3 mg/24 h, normal range: <250). Instrumental evaluation excluded intracranic calcifications, kidney stones and nephrocalcinosis. Serum calcium of first-degree relatives showed hypocalcemia in her father (8.1 mg/dl) and brother (8.2 mg/dl), and normocalcemia in her mother (9.6 mg/dl). Genomic DNA of the proband and her family members was isolated from peripheral blood leukocytes and the entire coding region and exon-intron boundaries of the CaSR gene were directly sequenced. Mutational analysis revealed a novel heterozygous variant of the CaSR gene in the proband, leading to the substitution of serine to proline at codon 591 in exon 7 (S591P), localized in the CaSR extracellular domain where >85% of activating mutations occurs. All affected relatives carried the same alteration that was absent in her mother and in 100 chromosomes of unrelated healthy subjects. In silico tests, using Mutation Taster software that integrates data from different databases, predicted a probably deleterious effect of the detected variant. In conclusion, we identified a novel missense variant in the CaSR gene co-segregating with hypocalcemia.
Volume 56
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more