Novel calcium-sensing receptor cytoplasmic tail deletion mutation causing autosomal dominant hypocalcemia: molecular and clinical study

European Journal of Endocrinology
Barbora ObermannovaGeoffrey N Hendy

Abstract

Autosomal dominant hypocalcemia (ADH) is a rare disorder caused by activating mutations of the calcium-sensing receptor (CASR). The treatment of ADH patients with 1α-hydroxylated vitamin D derivatives can cause hypercalciuria leading to nephrocalcinosis. We studied a girl who presented with hypoparathyroidism and asymptomatic hypocalcemia at age 2.5 years. Mutations of CASR were investigated by DNA sequencing. Functional analyses of mutant and WT CASRs were done in transiently transfected human embryonic kidney (HEK293) cells. The proband and her father are heterozygous for an eight-nucleotide deletion c.2703_2710delCCTTGGAG in the CASR encoding the intracellular domain of the protein. Transient expression of CASR constructs in kidney cells in vitro suggested greater cell surface expression of the mutant receptor with a left-shifted extracellular calcium dose-response curve relative to that of the WT receptor consistent with gain of function. Initial treatment of the patient with calcitriol led to increased urinary calcium excretion. Evaluation for mosaicism in the paternal grandparents of the proband was negative. We describe a novel naturally occurring deletion mutation within the CASR that apparently arose de novo in the fat...Continue Reading

References

May 26, 1995·The Journal of Biological Chemistry·J E GarrettF Fuller
Apr 15, 1993·Nature
Oct 10, 1996·The New England Journal of Medicine·S H PearceR V Thakker
May 20, 1999·American Journal of Human Genetics·S VerhoefA M van den Ouweland
Jun 19, 2001·American Journal of Human Genetics·M LeuerK Olek
Aug 14, 2003·The Journal of Clinical Endocrinology and Metabolism·Geoffrey N HendyDavid E C Cole
Jan 20, 2004·The Journal of Biological Chemistry·Yongfeng JiangMei Bai
Nov 9, 2004·The Journal of Clinical Endocrinology and Metabolism·Alfredo ScillitaniDavid E C Cole
Dec 14, 2004·Annals of Clinical Biochemistry·Ian R Gunn, Dairena Gaffney
Apr 13, 2006·The Journal of Clinical Endocrinology and Metabolism·Steven D MittelmanMitchell E Geffner
Dec 10, 2008·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Todd A ThemanKaren K Winer
Jan 1, 2009·Progress in Molecular Biology and Translational Science·Geoffrey N HendyLucie Canaff
Aug 28, 2010·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Ann StepanchickGerda E Breitwieser
Dec 12, 2012·Nature Genetics·M Andrew NesbitRajesh V Thakker
Jul 17, 2013·Best Practice & Research. Clinical Endocrinology & Metabolism·Gerda E Breitwieser
Dec 4, 2013·The Journal of Clinical Endocrinology and Metabolism·Yuka KinoshitaSeiji Fukumoto
May 15, 2015·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Bingzi DongToshio Matsumoto

❮ Previous
Next ❯

Citations

Sep 30, 2016·Frontiers in Physiology·Geoffrey N Hendy, Lucie Canaff
Jan 27, 2017·Orphanet Journal of Rare Diseases·C VaheM C Vantyghem

❮ Previous
Next ❯

Related Concepts

Related Feeds

Calcium & Bioenergetics

Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.