A Unifying Genetic Model for Facioscapulohumeral Muscular Dystrophy
Leiden University Medical Center · Centre National de la Recherche Scientifique · +9 more institutions
Abstract
Facioscapulohumeral muscular dystrophy (FSHD) is a common form of muscular dystrophy in adults that is foremost characterized by progressive wasting of muscles in the upper body. FSHD is associated with contraction of D4Z4 macrosatellite repeats on chromosome 4q35, but this contraction is pathogenic only in certain "permissive" chromosomal backgrounds. Here, we show that FSHD patients carry specific single-nucleotide polymorphisms in the chromosomal region distal to the last D4Z4 repeat. This FSHD-predisposing configuration creates a canonical polyadenylation signal for transcripts derived from DUX4, a double homeobox gene of unknown function that straddles the last repeat unit and the adjacent sequence.…
Citation impact
- FWCI
- 22.87
- Percentile
- 100%
- References
- 22
Authors
15- RJRichard J.L.F. Lemmers
Leiden University Medical Center
- PJPatrick J. van der Vliet
Leiden University Medical Center
- RKRinse Klooster
Leiden University Medical Center
- SSSabrina Sacconi
Centre National de la Recherche Scientifique, Laboratoire National de Référence
- PCPilar Camaño
Instituto de Salud Carlos III, Biomedical Research Networking Center on Neurodegenerative Diseases, Biogipuzkoa Health Research Institute
Topics & keywords
- Facioscapulohumeral muscular dystrophy
- Genetics
- Muscular dystrophy
- Biology
- Good health and well-being