Functional analysis reveals splicing mutations of the CASQ2 gene in patients with CPVT: implication for genetic counselling and clinical management.

Nathalie Roux-Buisson 1, 2 John Rendu 3 Isabelle Denjoy 4, 5 Pascale Guicheney 5, 6 Alice Goldenberg 7 Nadine David 8 Laurence Faivre 9 Olivier Barthez 10 Gian Antonio Danieli 11 Isabelle Marty 12 Joel Lunardi 3, * Julien Fauré 3
* Auteur correspondant
1 Laboratoire de biochimie et génétique moléculaire
2 Equipe AGIM3
3 INSERM U836, équipe 4, Muscles et pathologies
GIN - Grenoble Institut des Neurosciences, Laboratoire de biochimie et génétique moléculaire
4 Service de Cardiologie
5 Génétique, pharmacologie et physiopathologie des maladies cardiovasculaires
6 Génétique, pharmacologie et physiopathologie des maladies cardiovasculaires [Paris]
7 Service de génétique [Rouen]
8 Unité de cardiopédiatrie
9 Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon)
10 Service de cardiologie
11 Department of Biology
12 INSERM U836, équipe 4, Muscles et pathologies
GIN - Grenoble Institut des Neurosciences
Abstract : Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare and severe arrhythmogenic disorder. Although usually transmitted in a recessive form, few cases of dominant mutations have been reported. Thirteen mutations in the CASQ2 gene have been reported so far in association with CPVT. We performed molecular analysis of the CASQ2 gene in 43 probands with CPVT and identified eight mutations in five patients. Six mutations were novel: one was a single nucleotide deletion, three affected consensus splice sites, and two had unknown consequences: the c.939 + 5G>C and the synonymous c.381C>T variations. We demonstrated that these two variations affected CASQ2 splicing using a splicing minigene assay. These data increased significantly the number of CASQ2 mutations described in association with CPVT, revealed the high prevalence of splicing and truncating mutations in this gene and brought new insight regarding the dominant inheritance of the disease. Moreover, our report of the first splicing abnormalities in CASQ2 caused by intronic mutation or synonymous change underlines the absolute necessity to perform extensive molecular analysis for genetic diagnosis and counseling of CPVT.Hum Mutat 32:1-5, 2011. © 2011 Wiley-Liss, Inc.
Mots-clés : synonymous variations minigene CPVT calsequestrin 2
Type de document :
Article dans une revue
Human Mutation, Wiley, 2011, 32 (9), pp.995-999 〈10.1002/humu.21537〉
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https://www.hal.inserm.fr/inserm-00644146
Contributeur : Nathalie Roux-Buisson <>
Soumis le : jeudi 24 novembre 2011 - 09:37:08
Dernière modification le : vendredi 15 février 2019 - 13:58:11
Document(s) archivé(s) le : lundi 5 décembre 2016 - 00:30:32

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Nathalie Roux-Buisson, John Rendu, Isabelle Denjoy, Pascale Guicheney, Alice Goldenberg, et al.. Functional analysis reveals splicing mutations of the CASQ2 gene in patients with CPVT: implication for genetic counselling and clinical management.. Human Mutation, Wiley, 2011, 32 (9), pp.995-999 〈10.1002/humu.21537〉. 〈inserm-00644146〉

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