Mutational spectrum of DMD mutations in dystrophinopathy patients: Application of modern diagnostic techniques to a large cohort

Kevin M. Flanigan, Diane M. Dunn, Andrew Von Niederhausern, Payam Soltanzadeh, Eduard Gappmaier, Michael T. Howard, Jacinda B. Sampson, Jerry R. Mendell, Cheryl Wall, Wendy M. King, Alan Pestronk, Julaine M. Florence, Anne M. Connolly, Katherine D. Mathews, Carrie M. Stephan, Karla S. Laubenthal, Brenda L. Wong, Paula J. Morehart, Amy Meyer, Richard S. FinkelCarsten G. Bonnemann, Livija Medne, John W. Day, Joline C. Dalton, Marcia K. Margolis, Veronica J. Hinton, Robert B. Weiss, Mark Bromberg, Kathy Swoboda, Lynne Kerr, Olga Gurvich, Therese Tuohy, Laura Taylor, Ling Zhao, Kim Hart, Cybil Moural, Kate Hak, Bret Duval, Cindy Hamil, Maha Mahmoud, Alex Aoyagi, Laurence Viollet, Susan Gailey, Glenn Lopate, Paul Golumbek, Jeanine Schierbecker, Betsy Malkus, Catherine Siener, Kris Baldwin, Allan M. Glanzman, Jean Flickinger, Cameron E. Naughton

Research output: Contribution to journalArticlepeer-review

207 Scopus citations


Mutations in the DMD gene, encoding the dystrophin protein, are responsible for the dystrophinopathies Duchenne Muscular Dystrophy (DMD), Becker Muscular Dystrophy (BMD), and X-linked Dilated Cardiomyopathy (XLDC). Mutation analysis has traditionally been challenging, due to the large gene size (79 exons over 2.2Mb of genomic DNA). We report a very large aggregate data set comprised of DMD mutations detected in samples from patients enrolled in the United Dystrophinopathy Project, a multicenter research consortium, and in referral samples submitted for mutation analysis with a diagnosis of dystrophinopathy. We report 1,111 mutations in the DMD gene, including 891 mutations with associated phenotypes. These results encompass 506 point mutations (including 294 nonsense mutations) and significantly expand the number of mutations associated with the dystrophinopathies, highlighting the utility of modern diagnostic techniques. Our data supports the uniform hypermutability of CGA > TGA mutations, establishes the frequency of polymorphic muscle (Dp427m) protein isoforms and reveals unique genomic haplotypes associated with "private" mutations. We note that 60% of these patients would be predicted to benefit from skipping of a single DMD exon using antisense oligonucleotide therapy, and 62% would be predicted to benefit from an inclusive multiexonskipping approach directed toward exons 45 through 55.

Original languageEnglish
Pages (from-to)1657-1666
Number of pages10
JournalHuman mutation
Issue number12
StatePublished - Dec 2009


  • BMD
  • Becker muscular dystrophy
  • DMD
  • Duchenne muscular dystrophy
  • Dystrophinopathy
  • Mutation detection


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