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Null mutations causing depletion of the type 1 ryanodine receptor (RYR1) are commonly associated with recessive structural congenital myopathies with cores

2008; Wiley; Volume: 29; Issue: 5 Linguagem: Inglês

10.1002/humu.20696

1098-1004

Nicole Monnier, Isabelle Marty, Julien Fauré, Claudia Castiglioni, Claude Desnuelle, Sabrina Sacconi, B. Estournet, Ana Ferreiro, Norma B. Romero, Annie Laquerrière, Leïla Lazaro, Jean‐Jacques Martin, Éva Morava, Annick Rossi, Anneke J. van der Kooi, Marianne de Visser, Corien Verschuuren, Joël Lunardi,

Cellular transport and secretion

Human MutationVolume 29, Issue 5 p. 670-678 Research Article Null mutations causing depletion of the type 1 ryanodine receptor (RYR1) are commonly associated with recessive structural congenital myopathies with cores† Nicole Monnier, Nicole Monnier Laboratoire de Biochimie et Génétique Moléculaire and Centre de Référence des Maladies Neuro-Musculaires, CHU Grenoble, Grenoble, France INSERM U836, Grenoble Institut des Neurosciences, Grenoble, FranceSearch for more papers by this authorIsabelle Marty, Isabelle Marty INSERM U836, Grenoble Institut des Neurosciences, Grenoble, France Université Joseph Fourier, Grenoble, FranceSearch for more papers by this authorJulien Faure, Julien Faure Laboratoire de Biochimie et Génétique Moléculaire and Centre de Référence des Maladies Neuro-Musculaires, CHU Grenoble, Grenoble, France INSERM U836, Grenoble Institut des Neurosciences, Grenoble, France Université Joseph Fourier, Grenoble, FranceSearch for more papers by this authorClaudia Castiglioni, Claudia Castiglioni Servicio di Neurologia, Clinica Las Condes, Santiago, ChileSearch for more papers by this authorClaude Desnuelle, Claude Desnuelle Fédération des Maladies Neuromusculaires, CHU Nice, FranceSearch for more papers by this authorSabrina Sacconi, Sabrina Sacconi Fédération des Maladies Neuromusculaires, CHU Nice, FranceSearch for more papers by this authorBrigitte Estournet, Brigitte Estournet Hôpital Raymond Poincaré, Garches, FranceSearch for more papers by this authorAna Ferreiro, Ana Ferreiro Institut de Myologie and INSERM U582, Paris, FranceSearch for more papers by this authorNorma Romero, Norma Romero Institut de Myologie and INSERM U582, Paris, FranceSearch for more papers by this authorAnnie Laquerriere, Annie Laquerriere Service d'Anatomie et Cytologie Pathologique, CHU Rouen, FranceSearch for more papers by this authorLeila Lazaro, Leila Lazaro Département de Biochimie et Génétique Moléculaire, CHU Rennes, FranceSearch for more papers by this authorJean-Jacques Martin, Jean-Jacques Martin Instituut Born-Bunge, Universiteit Antwerpen, Antwerp, BelgiumSearch for more papers by this authorEva Morava, Eva Morava Department of Pediatrics, University Children's Hospital, Nijmegen, The NetherlandsSearch for more papers by this authorAnnick Rossi, Annick Rossi Unité de Génétique Clinique, CHU Rouen, FranceSearch for more papers by this authorAnneke Van der Kooi, Anneke Van der Kooi Department of Neurology, Academic Medical Centre, Amsterdam, The NetherlandsSearch for more papers by this authorMarianne de Visser, Marianne de Visser Department of Neurology, Academic Medical Centre, Amsterdam, The NetherlandsSearch for more papers by this authorCorien Verschuuren, Corien Verschuuren Clinical Genetics, University Medical Center, Groningen, The NetherlandsSearch for more papers by this authorJoël Lunardi, Corresponding Author Joël Lunardi jlunardi@chu-grenoble.fr Laboratoire de Biochimie et Génétique Moléculaire and Centre de Référence des Maladies Neuro-Musculaires, CHU Grenoble, Grenoble, France INSERM U836, Grenoble Institut des Neurosciences, Grenoble, France Université Joseph Fourier, Grenoble, FranceLaboratoire de Biochimie et Génétique Moléculaire, CHU Grenoble 217X, 38043 Grenoble Cedex, FranceSearch for more papers by this author Nicole Monnier, Nicole Monnier Laboratoire de Biochimie et Génétique Moléculaire and Centre de Référence des Maladies Neuro-Musculaires, CHU Grenoble, Grenoble, France INSERM U836, Grenoble Institut des Neurosciences, Grenoble, FranceSearch for more papers by this authorIsabelle Marty, Isabelle Marty INSERM U836, Grenoble Institut des Neurosciences, Grenoble, France Université Joseph Fourier, Grenoble, FranceSearch for more papers by this authorJulien Faure, Julien Faure Laboratoire de Biochimie et Génétique Moléculaire and Centre de Référence des Maladies Neuro-Musculaires, CHU Grenoble, Grenoble, France INSERM U836, Grenoble Institut des Neurosciences, Grenoble, France Université Joseph Fourier, Grenoble, FranceSearch for more papers by this authorClaudia Castiglioni, Claudia Castiglioni Servicio di Neurologia, Clinica Las Condes, Santiago, ChileSearch for more papers by this authorClaude Desnuelle, Claude Desnuelle Fédération des Maladies Neuromusculaires, CHU Nice, FranceSearch for more papers by this authorSabrina Sacconi, Sabrina Sacconi Fédération des Maladies Neuromusculaires, CHU Nice, FranceSearch for more papers by this authorBrigitte Estournet, Brigitte Estournet Hôpital Raymond Poincaré, Garches, FranceSearch for more papers by this authorAna Ferreiro, Ana Ferreiro Institut de Myologie and INSERM U582, Paris, FranceSearch for more papers by this authorNorma Romero, Norma Romero Institut de Myologie and INSERM U582, Paris, FranceSearch for more papers by this authorAnnie Laquerriere, Annie Laquerriere Service d'Anatomie et Cytologie Pathologique, CHU Rouen, FranceSearch for more papers by this authorLeila Lazaro, Leila Lazaro Département de Biochimie et Génétique Moléculaire, CHU Rennes, FranceSearch for more papers by this authorJean-Jacques Martin, Jean-Jacques Martin Instituut Born-Bunge, Universiteit Antwerpen, Antwerp, BelgiumSearch for more papers by this authorEva Morava, Eva Morava Department of Pediatrics, University Children's Hospital, Nijmegen, The NetherlandsSearch for more papers by this authorAnnick Rossi, Annick Rossi Unité de Génétique Clinique, CHU Rouen, FranceSearch for more papers by this authorAnneke Van der Kooi, Anneke Van der Kooi Department of Neurology, Academic Medical Centre, Amsterdam, The NetherlandsSearch for more papers by this authorMarianne de Visser, Marianne de Visser Department of Neurology, Academic Medical Centre, Amsterdam, The NetherlandsSearch for more papers by this authorCorien Verschuuren, Corien Verschuuren Clinical Genetics, University Medical Center, Groningen, The NetherlandsSearch for more papers by this authorJoël Lunardi, Corresponding Author Joël Lunardi jlunardi@chu-grenoble.fr Laboratoire de Biochimie et Génétique Moléculaire and Centre de Référence des Maladies Neuro-Musculaires, CHU Grenoble, Grenoble, France INSERM U836, Grenoble Institut des Neurosciences, Grenoble, France Université Joseph Fourier, Grenoble, FranceLaboratoire de Biochimie et Génétique Moléculaire, CHU Grenoble 217X, 38043 Grenoble Cedex, FranceSearch for more papers by this author First published: 11 April 2008 https://doi.org/10.1002/humu.20696Citations: 76 † Communicated by Claude Férec AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Mutations of the ryanodine receptor cause dominant and recessive forms of congenital myopathies with cores. Quantitative defects of RYR1 have been reported in families presenting with recessive forms of the disease and epigenic regulation has been recently proposed to explain potential maternal monoallelic silencing of the RYR1 gene. We investigated nine families presenting with a recessive form of the disease and showing a quantitative defect of RYR1 expression. Genetic analysis allowed the identification of a mutation on both alleles of the RYR1 gene for all patients, 15 being novel variants. We evidenced for all patients an alteration of the expression of the RYR1 gene caused by amorphic mutations responsible either for mRNA or protein instability. In seven families the variant present on the second allele was a missense mutation. In the remaining two families the second variant led to a hypomorphic expression of the RYR1 gene and was associated with a severe neonatal phenotype, pointing out the minimal amount of RYR1 needed for skeletal muscle function. Noticeably, a novel additional exon 3b was characterized in the most severely affected cases. This study showed that all cases presenting with a quantitative defect of RYR1 expression in our panel of patients affected by recessive core myopathies were caused by the presence of one recessive null allele and that variability of the phenotype depended on the nature of the mutation present on the second allele. Our study also indicated that presence of a second mutation must be investigated in sporadic cases or in dominant cases presenting with a familial clinical variability. Hum Mutat 29(5), 670–678, 2008. © 2008 Wiley-Liss, Inc. Citing Literature Supporting Information The Supplementary Material referred to in this article can be accessed at http://www.interscience.wiley.com/jpages/1059-7794/suppmat Filename Description HUMU20696_SuppMat.pdf199 KB Supporting Information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume29, Issue5May 2008Pages 670-678 RelatedInformation