Abstract
Autosomal dominant centronuclear myopathy is a rare congenital myopathy characterized by delayed motor milestones and muscular weakness. In 11 families affected by centronuclear myopathy, we identified recurrent and de novo missense mutations in the gene dynamin 2 (DNM2, 19p13.2), which encodes a protein involved in endocytosis and membrane trafficking, actin assembly and centrosome cohesion. The transfected mutants showed reduced labeling in the centrosome, suggesting that DNM2 mutations might cause centronuclear myopathy by interfering with centrosome function.
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Acknowledgements
We thank the affected individuals and their families for their participation in this study, J.P. Leroy and J.L. Mandel for continuous support, E. Ralston for comments and suggestions on the manuscript, A. Rouche for assistance with immunohistochemistry and C. Lacroix for providing a DNA sample. This work was supported by the Institut National de la Santé et de la Recherche Médicale, the Centre National de la Recherche Scientifique, the Hôpital Universitaire de Strasbourg, the Collège de France and the Association Française contre les Myopathies. H.L. is member of the German Muscular Dystrophy Network supported by the German Ministry of Education and Research. P.-Y.J. was a recipient of a fellowship from the Swiss Foundation for Research on Muscle Diseases. A.H.B. was supported by a grant from the US National Institutes of Health and the Joshua Frase Foundation. M.B. was the recipient of an Association Française contre les Myopathies fellowship.
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Supplementary information
Supplementary Fig. 1
Phenotype and haplotype analysis of 3 autosomal dominant CNM families and DNM2 genotyping. (PDF 502 kb)
Supplementary Fig. 2
Physical map of the CNM locus and DNM2 mutations. (PDF 593 kb)
Supplementary Fig. 3
Predicted DNM2 structure and multiple protein alignment. (PDF 425 kb)
Supplementary Table 1
Cumulative two-point lod scores for chromosome 19p13 markers. (PDF 53 kb)
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Bitoun, M., Maugenre, S., Jeannet, PY. et al. Mutations in dynamin 2 cause dominant centronuclear myopathy. Nat Genet 37, 1207–1209 (2005). https://doi.org/10.1038/ng1657
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DOI: https://doi.org/10.1038/ng1657
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