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Master Thesis

Étude de variants du gène de la calséquestrine de type 2 (Casq2)

Abstract : Cardiac calsequestrin (Casq2) is the major calcium storage protein in the sarcoplasmic reticulum of cardiomyocytes. It is involved in catecholaminergic polymorphic ventricular tachycardia, a severe inherited arrythmogenic disorder. CASQ2 mutations identified from 2007 to 2013 in the Molecular Genetic Laboratory of Grenoble were gathered and splicing effects of intronic and missense mutations were evaluated with prediction softwares. Functionnal analysis of two CASQ2 mutations was performed: p.S15C, a missense mutation in the signal peptide, and c.838+88T>G, a deep intronic mutation possibly involved in splicing defect. In silico predictions did not detect any splicing effect for the missense mutations but half of the mutations identified in the laboratory were shown to affect CASQ2 splicing. Wild-type and mutant c.838+88T>G minigene in vitro analysis showed no splicing defect. Wild-type and p.S15C mutant were analyzed after cell line transfections. Immunofluorescence studies, immunoblots, and glycosylation studies showed no effect of the p.S15C mutation. Polymerization studies suggested a dimerization defect for the mutant protein, although this results needs to be confirmed. In conclusion, these results could not prove the pathogenicity of the p.S15C and c.838+88T>G mutations but allowed the validation of new tools for further functional analysis in the laboratory.
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Master Thesis
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Contributor : Jean-Hugues Morneau <>
Submitted on : Monday, November 4, 2013 - 9:16:49 AM
Last modification on : Tuesday, May 11, 2021 - 11:36:17 AM
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  • HAL Id : dumas-00879469, version 1


Guillaume Sarrabay. Étude de variants du gène de la calséquestrine de type 2 (Casq2). Médecine humaine et pathologie. 2013. ⟨dumas-00879469⟩



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