Novel activating mutation of human calcium-sensing receptor in a family with autosomal dominant hypocalcaemia

Molecular and Cellular Endocrinology
Natalia BaranUdo Schmitz

Abstract

Autosomal dominant hypocalcaemia (ADH) is caused by activating mutations in the calcium sensing receptor gene (CaR) and characterised by mostly asymptomatic mild to moderate hypocalcaemia with low, inappropriately serum concentration of PTH. The purpose of the present study was to biochemically and functionally characterise a novel mutation of CaR. A female proband presenting with hypocalcaemia was diagnosed to have "idiopathic hypoparathyroidism" at the age of 10 with a history of muscle pain and cramps. Further examinations demonstrated hypocalcaemia in nine additional family members, affecting three generations. P136L CaR mutation was predicted to cause gain of function of CaR. Affected family members showed relevant hypocalcaemia (mean ± SD; 1.9 ± 0.1 mmol/l). Patient history included mild seizures and recurrent nephrolithiasis. Genetic analysis confirmed that hypocalcaemia cosegregated with a heterozygous mutation at codon 136 (CCC → CTC/Pro → Leu) in exon 3 of CaR confirming the diagnosis of ADH. For in vitro studies P136L mutant CaR was generated by site-directed mutagenesis and examined in transiently transfected HEK293 cells. Extracellular calcium stimulation of transiently transfected HEK293 cells showed significantly...Continue Reading

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Citations

Aug 27, 2016·Molecular and Cellular Endocrinology·Katia MarucaStefano Mora
May 31, 2018·The Journal of Clinical Endocrinology and Metabolism·Branca M CavacoGeoffrey N Hendy
May 3, 2019·The New England Journal of Medicine·Rachel I Gafni, Michael T Collins
Jun 10, 2020·BMJ Case Reports·Vânia GomesMaria João Guerreiro Martins Bugalho
Sep 3, 2020·Annals of Pediatric Endocrinology & Metabolism·Jung Eun MoonCheol Woo Ko

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