Journal article
Nonsense mutation-associated Becker muscular dystrophy: interplay between exon definition and splicing regulatory elements within the DMD gene
Human mutation, Vol.32(3), pp.299-308
03/2011
DOI: 10.1002/humu.21426
PMCID: PMC3724403
PMID: 21972111
Abstract
Nonsense mutations are usually predicted to function as null alleles due to premature termination of protein translation. However, nonsense mutations in the
DMD
gene, encoding the dystrophin protein, have been associated with both the severe Duchenne Muscular Dystrophy (DMD) and milder Becker Muscular Dystrophy (BMD) phenotypes. In a large survey, we identified 243 unique nonsense mutations in the
DMD
gene, and for 210 of these we could establish definitive phenotypes. We analyzed the reading frame predicted by exons flanking those in which nonsense mutations were found, and present evidence that nonsense mutations resulting in BMD likely do so by inducing exon skipping, confirming that exonic point mutations affecting exon definition have played a significant role in determining phenotype. We present a new model based on the combination of exon definition and intronic splicing regulatory elements for the selective association of BMD nonsense mutations with a subset of
DMD
exons prone to mutation-induced exon skipping.
Details
- Title: Subtitle
- Nonsense mutation-associated Becker muscular dystrophy: interplay between exon definition and splicing regulatory elements within the DMD gene
- Creators
- Kevin M Flanigan - Center for Gene Therapy, Nationwide Children’s Hospital, Columbus, OhioDiane M 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 Neurology, 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 B Sampson - Department of Neurology, University of Utah School of Medicine, Salt Lake City, UtahKathryn J Swoboda - Department of Neurology, University of Utah School of Medicine, Salt Lake City, UtahMark B Bromberg - Department of Neurology, University of Utah School of Medicine, Salt Lake City, UtahJerry R Mendell - Center for Gene Therapy, Nationwide Children’s Hospital, Columbus, OhioLaura Taylor - Center for Gene Therapy, Nationwide Children’s Hospital, Columbus, OhioChristine B Anderson - Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UtahAlan Pestronk - Department of Neurology, Washington University at St. Louis, St. Louis, MissouriJulaine Florence - Department of Neurology, Washington University at St. Louis, St. Louis, MissouriAnne M Connolly - Department of Neurology, Washington University at St. Louis, St. Louis, MissouriKatherine D Mathews - Department of Pediatrics, University of Iowa, Iowa City, IowaBrenda Wong - Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OhioRichard S Finkel - Department of Neurology, The Children’s Hospital of Philadelphia, Philadelphia, PennsylvaniaCarsten G Bonnemann - Department of Neurology, The Children’s Hospital of Philadelphia, Philadelphia, PennsylvaniaJohn W Day - Department of Neurology, University of Minnesota, Minneapolis, MinnesotaCraig McDonald - Department of Physical Medicine and Rehabilitation, University of California Davis, Sacramento, CaliforniaRobert 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.32(3), pp.299-308
- DOI
- 10.1002/humu.21426
- PMID
- 21972111
- PMCID
- PMC3724403
- NLM abbreviation
- Hum Mutat
- ISSN
- 1059-7794
- eISSN
- 1098-1004
- Language
- English
- Date published
- 03/2011
- Academic Unit
- Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
- Record Identifier
- 9984020618802771
Metrics
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