Abstract
The autosomal dominant myopathy facioscapulohumeral muscular dystrophy (FSHD1, OMIM 158900) is caused by contraction of the D4Z4 repeat array on 4qter. We show that this contraction causes marked hypomethylation of the contracted D4Z4 allele in individuals with FSHD1. Individuals with phenotypic FSHD1, who are clinically identical to FSHD1 but have an unaltered D4Z4, also have hypomethylation of D4Z4. These results strongly suggest that hypomethylation of D4Z4 is a key event in the cascade of epigenetic events causing FSHD1.
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Acknowledgements
We dedicate this work to the memory of Lodewijk Sandkuijl, who unexpectedly passed away during preparation of this manuscript. We thank R. ten Hove for contributing to the development of the methylation assays and C. Wijmenga and D. Smeets for providing material from individuals with ICF. Our FSHD research is made possible by the Prinses Beatrix Fonds, the Muscular Dystrophy Association USA, the FSH Society, the Stichting FSHD, the Shaw Family and the US National Institutes of Health.
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van Overveld, P., Lemmers, R., Sandkuijl, L. et al. Hypomethylation of D4Z4 in 4q-linked and non-4q-linked facioscapulohumeral muscular dystrophy. Nat Genet 35, 315–317 (2003). https://doi.org/10.1038/ng1262
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DOI: https://doi.org/10.1038/ng1262
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