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Type 1 FSHD with 6–10 Repeated Units: Factors Underlying Severity in Index Cases and Disease Penetrance in Their Relatives Attention

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Reference Center of Neuromuscular disorders and ALS, Timone University Hospital, AP-HM, 264 rue Saint-Pierre, Cedex 05 13385 Marseille, France
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Medical Genetics, Aix Marseille Université—Inserm UMR_1251, 13005 Marseille, France
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Service de Neurologie et d’explorations fonctionnelles, Centre Hospitalier Universitaire de Toulouse, 31000 Toulouse, France
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Reference Center of Neuromuscular Disorders AOC, Bordeaux University Hospitals, 33000 Bordeaux, France
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Electroneuromyography and Neuromuscular Department, GHE Neurologic Hospital, Cedex 69677 Lyon-Bron, France
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Neurogenetic Department, GHN Croix-Rousse Hospital, 69004 Lyon, France
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Neuromuscular Disease Specialized Center, Nice University Hospital, 06000 Nice, France
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Neurology Department, APHP, CHU de Bicêtre, 78 rue du Général Leclerc, Cedex 94276 Le Kremlin-Bicêtre, France
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Nerve-Muscle Unit, Department of Clinical Neurosciences, Lausanne University, Hospital (CHUV), Lausanne 1002, Switzerland
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(6), 2221; https://doi.org/10.3390/ijms21062221
Received: 27 January 2020 / Revised: 20 March 2020 / Accepted: 21 March 2020 / Published: 23 March 2020
(This article belongs to the Special Issue Epigenetic Alterations in Neuromuscular Disorders)
Molecular defects in type 1 facioscapulohumeral muscular dystrophy (FSHD) are caused by a heterozygous contraction of the D4Z4 repeat array from 1 to 10 repeat units (RUs) on 4q35. This study compared (1) the phenotype and severity of FSHD1 between patients carrying 6–8 vs. 9–10 RUs, (2) the amount of methylation in different D4Z4 regions between patients with FSHD1 with different clinical severity scores (CSS). This cross-sectional multicenter study was conducted to measure functional scales and for genetic analysis. Patients were classified into two categories according to RUs: Group 1, 6–8; Group 2, 9–10. Methylation analysis was performed in 27 patients. A total of 99 carriers of a contracted D4Z4 array were examined. No significant correlations between RUs and CSS (r = 0.04, p = 0.73) and any of the clinical outcome scales were observed between the two groups. Hypomethylation was significantly more pronounced in patients with high CSS (>3.5) than those with low CSS (<1.5) (in DR1 and 5P), indicating that the extent of hypomethylation might modulate disease severity. In Group 1, the disease severity is not strongly correlated with the allele size and is mostly correlated with the methylation of D4Z4 regions. View Full-Text
Keywords: Facioscapulohumeral muscular dystrophy; FSHD; phenotype; genotype; association; correlation; methylation Facioscapulohumeral muscular dystrophy; FSHD; phenotype; genotype; association; correlation; methylation
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Salort-Campana, E.; Fatehi, F.; Beloribi-Djefaflia, S.; Roche, S.; Nguyen, K.; Bernard, R.; Cintas, P.; Solé, G.; Bouhour, F.; Ollagnon, E.; Sacconi, S.; Echaniz-Laguna, A.; Kuntzer, T.; Levy, N.; Magdinier, F.; Attarian, S. Type 1 FSHD with 6–10 Repeated Units: Factors Underlying Severity in Index Cases and Disease Penetrance in Their Relatives Attention. Int. J. Mol. Sci. 2020, 21, 2221.

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