Journal article
Mutational Spectrum of DMD Mutations in Dystrophinopathy Patients: Application of Modern Diagnostic Techniques to a Large Cohort
Human mutation, Vol.30(12), pp.1657-1666
12/2009
DOI: 10.1002/humu.21114
PMCID: PMC3404892
PMID: 19937601
Abstract
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 2.2 Mb 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 1111 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 multi-exon skipping approach directed toward exons 45 through 55.
Details
- Title: Subtitle
- Mutational Spectrum of DMD Mutations in Dystrophinopathy Patients: Application of Modern Diagnostic Techniques to a Large Cohort
- Creators
- Kevin M Flanigan - Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UtahDiane Dunn - Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UtahAndrew von Niederhausern - Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UtahPayam Soltanzadeh - Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UtahEduard Gappmaier - Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UtahMichael T Howard - Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UtahJacinda Sampson - Department of Neurology, University of Utah School of Medicine, Salt Lake City, UtahJerry Mendell - Department of Neurology, Columbus Children's Hospital, Columbus, OhioCheryl Wall - Department of Neurology, Columbus Children's Hospital, Columbus, OhioWendy King - Department of Neurology, Columbus Children's Hospital, Columbus, OhioAlan Pestronk - Department of Neurology, Washington University at St. Louis, St. Louis, MissouriJulaine Florence - Department of Neurology, Washington University at St. Louis, St. Louis, MissouriAnne Connolly - Department of Neurology, Washington University at St. Louis, St. Louis, MissouriKatherine D Mathews - Department of Pediatrics, University of Iowa, Iowa City, IowaCarrie Stephan - Department of Pediatrics, University of Iowa, Iowa City, IowaKarla Laubenthal - Department of Pediatrics, University of Iowa, Iowa City, IowaBrenda Wong - Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OhioPaula Morehart - Department of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OhioAmy Meyer - Department of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OhioRichard Finkel - Department of Neurology, The Children's Hospital of Philadelphia, Philadelphia, PennsylvaniaCarsten G Bonnemann - Department of Neurology, The Children's Hospital of Philadelphia, Philadelphia, PennsylvaniaLivija Medne - Department of Neurology, The Children's Hospital of Philadelphia, Philadelphia, PennsylvaniaJohn W Day - Department of Neurology, University of Minnesota, Minneapolis, MinnesotaJoline C Dalton - Department of Neurology, University of Minnesota, Minneapolis, MinnesotaMarcia Margolis - Department of Neurology, University of Minnesota, Minneapolis, MinnesotaVeronica Hinton - Columbia-Presbyterian Hospital, New York, New YorkRobert B Weiss - Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah
- Resource Type
- Journal article
- Publication Details
- Human mutation, Vol.30(12), pp.1657-1666
- DOI
- 10.1002/humu.21114
- PMID
- 19937601
- PMCID
- PMC3404892
- NLM abbreviation
- Hum Mutat
- ISSN
- 1059-7794
- eISSN
- 1098-1004
- Language
- English
- Date published
- 12/2009
- Academic Unit
- Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
- Record Identifier
- 9984013203002771
Metrics
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