Journal article
Clinical and genetic characterization of manifesting carriers of DMD mutations
Neuromuscular disorders : NMD, Vol.20(8), pp.499-504
2010
DOI: 10.1016/j.nmd.2010.05.010
PMCID: PMC2944769
PMID: 20630757
Abstract
Manifesting carriers of
DMD gene mutations may present diagnostic challenges, particularly in the absence of a family history of dystrophinopathy. We review the clinical and genetic features in 15 manifesting carriers identified among 860 subjects within the United Dystrophinopathy Project, a large clinical dystrophinopathy cohort whose members undergo comprehensive
DMD mutation analysis. We defined manifesting carriers as females with significant weakness, excluding those with only myalgias/cramps. DNA extracted from peripheral blood was used to study X-chromosome inactivation patterns. Among these manifesting carriers, age at symptom onset ranged from 2 to 47
years. Seven had no family history and eight had male relatives with Duchenne muscular dystrophy (DMD). Clinical severity among the manifesting carriers varied from a DMD-like progression to a very mild Becker muscular dystrophy-like phenotype. Eight had exonic deletions or duplications and six had point mutations. One patient had two mutations (an exonic deletion and a splice site mutation), consistent with a heterozygous compound state. The X-chromosome inactivation pattern was skewed toward non-random in four out of seven informative deletions or duplications but was random in all cases with nonsense mutations. We present the results of
DMD mutation analysis in this manifesting carrier cohort, including the first example of a presumably compound heterozygous
DMD mutation. Our results demonstrate that improved molecular diagnostic methods facilitate the identification of
DMD mutations in manifesting carriers, and confirm the heterogeneity of mutational mechanisms as well as the wide spectrum of phenotypes.
Details
- Title: Subtitle
- Clinical and genetic characterization of manifesting carriers of DMD mutations
- Creators
- Payam Soltanzadeh - Department of Human Genetics, University of Utah, Salt Lake City, UT, USAMichael J Friez - Molecular Diagnostic Laboratory, Greenwood Genetic Center, Greenwood, SC, USADiane Dunn - Department of Human Genetics, University of Utah, Salt Lake City, UT, USAAndrew von Niederhausern - Department of Human Genetics, University of Utah, Salt Lake City, UT, USAOlga L Gurvich - Department of Human Genetics, University of Utah, Salt Lake City, UT, USAKathryn J Swoboda - Department of Neurology, University of Utah, Salt Lake City, UT, USAJacinda B Sampson - Department of Neurology, University of Utah, Salt Lake City, UT, USAAlan Pestronk - Department of Neurology, Washington University, St. Louis, MO, USAAnne M Connolly - Department of Neurology, Washington University, St. Louis, MO, USAJulaine M Florence - Department of Neurology, Washington University, St. Louis, MO, USARichard S Finkel - Department of Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA, USACarsten G Bönnemann - Department of Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA, USALivija Medne - Department of Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA, USAJerry R Mendell - Center for Gene Therapy, Nationwide Children’s Hospital, Department of Pediatrics, Ohio State University, Columbus, OH, USAKatherine D Mathews - Department of Pediatrics, University of Iowa, Iowa City, IA, USABrenda L Wong - Departments of Neurology and Pediatrics, Cincinnati Children’s Hospital, Cincinnati, OH, USAMichael D Sussman - Department of Orthopedic Surgery, Shriners Hospital for Children, Portland, OR, USAJonathan Zonana - Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USAKaren Kovak - Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USASidney M Gospe Jr - Departments of Neurology and Pediatrics, University of Washington, Division of Pediatric Neurology, Seattle Children’s Hospital, Seattle, WA, USAEduard Gappmaier - Department of Physical Therapy, University of Utah, Salt Lake City, UT, USALaura E Taylor - Center for Gene Therapy, Nationwide Children’s Hospital, Department of Pediatrics, Ohio State University, Columbus, OH, USAMichael T Howard - Department of Human Genetics, University of Utah, Salt Lake City, UT, USARobert B Weiss - Department of Human Genetics, University of Utah, Salt Lake City, UT, USAKevin M Flanigan - Center for Gene Therapy, Nationwide Children’s Hospital, Department of Pediatrics, Ohio State University, Columbus, OH, USA
- Resource Type
- Journal article
- Publication Details
- Neuromuscular disorders : NMD, Vol.20(8), pp.499-504
- DOI
- 10.1016/j.nmd.2010.05.010
- PMID
- 20630757
- PMCID
- PMC2944769
- NLM abbreviation
- Neuromuscul Disord
- ISSN
- 0960-8966
- eISSN
- 1873-2364
- Publisher
- Elsevier B.V
- Language
- English
- Date published
- 2010
- Academic Unit
- Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
- Record Identifier
- 9984020794102771
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