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Clinical features of facioscapulohumeral muscular dystrophy 2

Item Type:Article
Title:Clinical features of facioscapulohumeral muscular dystrophy 2
Creators Name:de Greef, J.C. and Lemmers, R.J. and Camano, P. and Day, J.W. and Sacconi, S. and Dunand, M. and van Engelen, B.G. and Kiuru-Enari, S. and Padberg, G.W. and Rosa, A.L. and Desnuelle, C. and Spuler, S. and Tarnopolsky, M. and Venance, S.L. and Frants, R.R. and van der Maarel, S.M. and Tawil, R.
Abstract:OBJECTIVE: In some 5% of patients with facioscapulohumeral muscular dystrophy (FSHD), no D4Z4 repeat contraction on chromosome 4q35 is observed. Such patients, termed patients with FSHD2, show loss of DNA methylation and heterochromatin markers at the D4Z4 repeat that are similar to patients with D4Z4 contractions (FSHD1). This commonality suggests that a change in D4Z4 chromatin structure unifies FSHD1 and FSHD2. The aim of our study was to critically evaluate the clinical features in patients with FSHD2 in order to establish whether these patients are phenotypically identical to FSHD1 and to establish the effects of the (epi-) genotype on the phenotype. METHODS: This cross-sectional study studied 33 patients with FSHD2 from 27 families, the largest cohort described to date. All patients were clinically assessed using a standardized clinical evaluation form. Genotype analysis was performed by pulsed field gel electrophoresis and PCR; D4Z4 methylation was studied by methylation-sensitive Southern blot analysis. RESULTS: FSHD2 is identical to FSHD1 in its clinical presentation. Notable differences include a higher incidence (67%) of sporadic cases and the absence of gender differences in disease severity in FSHD2. Overall, average disease severity in FSHD2 was similar to that reported in FSHD1 and was not influenced by D4Z4 repeat size. In FSHD2, a small effect of the degree of hypomethylation on disease severity was observed. CONCLUSIONS: Clinically, patients with FSHD2 are indistinguishable from patients with FSHD1. The present data suggest that FSHD1 and FSHD2 are the result of the same pathophysiologic process.
Keywords:Pair 4 Human Chromosomes, Cohort Studies, Cross-Sectional Studies, DNA Methylation, DNA Repeat Expansion, Family Health, Genotype, Facioscapulohumeral Muscular Dystrophy, Nuclear Proteins, Phenotype, Genetic Polymorphism
Publisher:American Academy of Neurology
Page Range:1548-1554
Date:26 October 2010
Official Publication:https://doi.org/10.1212/WNL.0b013e3181f96175
PubMed:View item in PubMed

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