Abstract
Emery–Dreifuss muscular dystrophy (EDMD) is a neuromuscular disorder exhibiting a cardiomyopathy with cardiac conduction defects. X-linked EDMD arises from mutations in the EMD gene, which encodes for a nuclear membrane protein termed emerin. In this study, we describe novel and recurrent EMD mutations identified in 18 probands and three carriers from a cohort of 255 North American patients referred for EDMD genetic mutation analysis. Eight of these mutations are novel including six frameshift mutations (p.D9GfsX24, p.F39SfsX17, p.R45KfsX16, p.F190YfsX19, p.R203PfsX34 and p.R204PfsX7) and two non-sense mutations (p.S143X, p.W200X). Our data augment the number of EMD mutations by 13.8%, equating to an increase of 5.2% in the total known EMD mutations and to an increase of 6.0% in the number of different mutations. Analysis of the exon distribution of mutations within the EMD gene, suggests a nonrandom distribution, with exon 2 as a hot spot. This phenomenon may be due to its high GC content, which at 60% is the most GC-rich exon in the EMD gene.
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Acknowledgements
We wish to thank the curators of the UMD-EMD database, Gisele Bonne and Rabah Ben Yaou for their guidance on how to extract data contained with it. This work was supported by grant No. A6356678101 from the Muscular Dystrophy Association, awarded to JAE and CAB. JS was partially funded by the MYORES Network of Excellence (contract 511978) from the European Commission 6th Framework Programme. The laboratory of PSZ is also supported by The Muscular Dystrophy Campaign, the Association of International Cancer Research, Association Française contre les Myopathies, The Wellcome Trust and OPTISTEM (contract 223098), through the European Union 7th Framework Programme.
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Brown, C., Scharner, J., Felice, K. et al. Novel and recurrent EMD mutations in patients with Emery–Dreifuss muscular dystrophy, identify exon 2 as a mutation hot spot. J Hum Genet 56, 589–594 (2011). https://doi.org/10.1038/jhg.2011.65
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DOI: https://doi.org/10.1038/jhg.2011.65
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