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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Early onset collagen VI myopathies: Genetic and clinical correlations
Annals of Neurology, Volume 68, No. 4, Year 2010
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Description
Objective Mutations in the genes encoding the extracellular matrix protein collagen VI (ColVI) cause a spectrum of disorders with variable inheritance including Ullrich congenital muscular dystrophy, Bethlem myopathy, and intermediate phenotypes. We extensively characterized, at the clinical, cellular, and molecular levels, 49 patients with onset in the first 2 years of life to investigate genotype-phenotype correlations. Methods Patients were classified into 3 groups: early-severe (18%), moderate-progressive (53%), and mild (29%). ColVI secretion was analyzed in patient-derived skin fibroblasts. Chain-specific transcript levels were quantified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and mutation identification was performed by sequencing of complementary DNA. Results ColVI secretion was altered in all fibroblast cultures studied. We identified 56 mutations, mostly novel and private. Dominant de novo mutations were detected in 61% of the cases. Importantly, mutations causing premature termination codons (PTCs) or in-frame insertions strikingly destabilized the corresponding transcripts. Homozygous PTC-causing mutations in the triple helix domains led to the most severe phenotypes (ambulation never achieved), whereas dominant de novo in-frame exon skipping and glycine missense mutations were identified in patients of the moderate-progressive group (loss of ambulation). Interpretation This work emphasizes that the diagnosis of early onset ColVI myopathies is arduous and time-consuming, and demonstrates that quantitative RT-PCR is a helpful tool for the identification of some mutation-bearing genes. Moreover, the clinical classification proposed allowed genotype-phenotype relationships to be explored, and may be useful in the design of future clinical trials. © 2010 American Neurological Association.
Authors & Co-Authors
Briñas, Laura
France, Paris
Inserm
France, Paris
Sorbonne Université
Richard, Pascale
France, Paris
Inserm
France, Paris
Sorbonne Université
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Quijano-Roy, Susana
France, Paris
Inserm
France, Paris
Sorbonne Université
France, Garches
Hopital Raymond Poincare
Gartioux, Corine
France, Paris
Inserm
France, Paris
Sorbonne Université
Ledeuil, Céline
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Lacene, Emmanuelle
France, Paris
Inserm
France, Paris
Sorbonne Université
Makri, Samira
Algeria, Algiers
Etablissement Hospitalier Spécialisé Ali Ait Idir
Ferreiro, Ana
France, Paris
Inserm
France, Paris
Sorbonne Université
France, Garches
Hopital Raymond Poincare
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Maugenre, Svetlana
France, Paris
Inserm
France, Paris
Sorbonne Université
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Topaloglu, Haluk A.
Turkey, Ankara
Hacettepe Üniversitesi
Haliloglu, Göknur
Turkey, Ankara
Hacettepe Üniversitesi
Pénisson-Besnier, Isabelle
France, Angers
Chu Angers
Jeannet, Pierre Yves
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Merlini, Luciano
Italy, Ferrara
University of Ferrara
Italy, Bologna
Irccs Rizzoli Orthopaedic Institute, Bologna
Navarro, Carmen A.
Spain, Vigo
Universidade de Vigo
Toutain, Annick M.
France, Tours
Hopital Bretonneau
Chaigne, Denys
France, Strasbourg
Clinique Sainte-odile
Desguerre, Isabelle
France, Paris
Hôpital Necker Enfants Malades
France, Creteil
Université Paris-est Créteil Val de Marne
De Die-Smulders, Christine
Netherlands, Maastricht
Maastricht Universitair Medisch Centrum+
Dunand, Murielle
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Échenne, Bernard B.
France, Montpellier
Hopital Gui de Chauliac
Eymard, Bruno
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Kuntzer, Thierry
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Maincent, K.
France, Paris
Hôpital Armand-trousseau
Mayer, Michèle
France, Paris
Hôpital Armand-trousseau
Plessis, Ghislaine
France, Caen
Hopital Clemenceau
Rivier, François
France, Montpellier
Hopital Gui de Chauliac
Roelens, F.
Belgium, Roeselare
Dominiek Savio Instituut Gits
Stojkovic, Tanya
France, Paris
Hôpital Universitaire Pitié Salpêtrière
France, Paris
Sorbonne Université
Lía Taratuto, Ana
Argentina, Buenos Aires
Fundacion Para la Lucha Contra Las Enfermedades Neurologicas de la Infancia
Lubieniecki, Fabiana
Argentina, Buenos Aires
Pediatric Hospital
Monges, Soledad
Argentina, Buenos Aires
Pediatric Hospital
Tranchant, Christine H.
France, Strasbourg
Les Hôpitaux Universitaires de Strasbourg
Viollet, Louis
France, Garches
Hopital Raymond Poincare
France, Paris
Hôpital Necker Enfants Malades
Roméro, Norma Beatriz
France, Paris
Inserm
France, Paris
Sorbonne Université
Estournet-Mathiaud, Brigitte
France, Garches
Hopital Raymond Poincare
Guicheney, Pascale
France, Paris
Inserm
France, Paris
Sorbonne Université
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Allamand, Valérie
France, Paris
Inserm
France, Paris
Sorbonne Université
Statistics
Citations: 115
Authors: 38
Affiliations: 23
Identifiers
Doi:
10.1002/ana.22087
ISSN:
03645134
e-ISSN:
15318249
Research Areas
Cancer
Disability
Genetics And Genomics
Health System And Policy
Maternal And Child Health
Study Approach
Quantitative