دورية أكاديمية
Natural history of Charcot-Marie-Tooth disease type 2A: a large international multicentre study.
| العنوان: | Natural history of Charcot-Marie-Tooth disease type 2A: a large international multicentre study. |
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| المؤلفون: | Pipis, Menelaos, Feely, Shawna ME, Polke, James M, Skorupinska, Mariola, Perez, Laura, Shy, Rosemary R, Laura, Matilde, Morrow, Jasper M, Moroni, Isabella, Pisciotta, Chiara, Taroni, Franco, Vujovic, Dragan, Lloyd, Thomas E, Acsadi, Gyula, Yum, Sabrina W, Lewis, Richard A, Finkel, Richard S, Herrmann, David N, Day, John W, Li, Jun, Saporta, Mario, Sadjadi, Reza, Walk, David, Burns, Joshua, Muntoni, Francesco, Ramchandren, Sindhu, Horvath, Rita, Johnson, Nicholas E, Züchner, Stephan, Pareyson, Davide, Scherer, Steven S, Rossor, Alexander M, Shy, Michael E, Reilly, Mary M, Inherited Neuropathies Consortium - Rare Disease Clinical Research Network (INC-RDCRN) |
| بيانات النشر: | //dx.doi.org/10.1093/brain/awaa323 Brain Oxford University Press (OUP) |
| سنة النشر: | 2020 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | Charcot-Marie-Tooth Examination Score v2.0, Charcot-Marie-Tooth disease type 2A, genotype-phenotype correlations, mitofusin-2, standardized response mean, Adolescent, Adult, Age of Onset, Charcot-Marie-Tooth Disease, Child, Preschool, Cohort Studies, Disease Progression, Female, GTP Phosphohydrolases, Genes, Dominant, Recessive, Genetic Association Studies, Genetic Markers, Humans, Infant, Longitudinal Studies, Male, Mitochondrial Proteins, Neurologic Examination, Orthotic Devices, Prognosis, Prospective Studies, Wheelchairs |
| الوصف: | Mitofusin-2 (MFN2) is one of two ubiquitously expressed homologous proteins in eukaryote cells, playing a critical role in mitochondrial fusion. Mutations in MFN2 (most commonly autosomal dominant) cause Charcot-Marie-Tooth disease type 2A (CMT2A), the commonest axonal form of CMT, with significant allelic heterogeneity. Previous, moderately-sized, cross sectional genotype-phenotype studies of CMT2A have described the phenotypic spectrum of the disease, but longitudinal natural history studies are lacking. In this large multicentre prospective cohort study of 196 patients with dominant and autosomal recessive CMT2A, we present an in-depth genotype-phenotype study of the baseline characteristics of patients with CMT2A and longitudinal data (1-2 years) to describe the natural history. A childhood onset of autosomal dominant CMT2A is the most predictive marker of significant disease severity and is independent of the disease duration. When compared to adult onset autosomal dominant CMT2A, it is associated with significantly higher rates of use of ankle-foot orthoses, full-time use of wheelchair, dexterity difficulties and also has significantly higher CMT Examination Score (CMTESv2) and CMT Neuropathy Score (CMTNSv2) at initial assessment. Analysis of longitudinal data using the CMTESv2 and its Rasch-weighted counterpart, CMTESv2-R, show that over 1 year, the CMTESv2 increases significantly in autosomal dominant CMT2A (mean change 0.84 ± 2.42; two-tailed paired t-test P = 0.039). Furthermore, over 2 years both the CMTESv2 (mean change 0.97 ± 1.77; two-tailed paired t-test P = 0.003) and the CMTESv2-R (mean change 1.21 ± 2.52; two-tailed paired t-test P = 0.009) increase significantly with respective standardized response means of 0.55 and 0.48. In the paediatric CMT2A population (autosomal dominant and autosomal recessive CMT2A grouped together), the CMT Pediatric Scale increases significantly both over 1 year (mean change 2.24 ± 3.09; two-tailed paired t-test P = 0.009) and over 2 years (mean change 4.00 ± 3.79; ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | Print; application/pdf |
| اللغة: | English |
| العلاقة: | https://www.repository.cam.ac.uk/handle/1810/311582Test |
| DOI: | 10.17863/CAM.58674 |
| الإتاحة: | https://doi.org/10.17863/CAM.58674Test https://www.repository.cam.ac.uk/handle/1810/311582Test |
| حقوق: | Attribution-NonCommercial-NoDerivatives 4.0 International ; https://creativecommons.org/licenses/by-nc-nd/4.0Test/ |
| رقم الانضمام: | edsbas.7EF9DE73 |
| قاعدة البيانات: | BASE |
| DOI: | 10.17863/CAM.58674 |
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