Journal article
Early-progressive dilated cardiomyopathy in a family with Becker muscular dystrophy related to a novel frameshift mutation in the dystrophin gene exon 27
Journal of human genetics, Vol.60(3), pp.151-155
03/2015
DOI: 10.1038/jhg.2014.112
PMCID: PMC4374993
PMID: 25537791
Abstract
We report a family in which two male siblings with Becker muscular dystrophy (BMD) developed severe dilated cardiomyopathy (DCM) and progressive heart failure (HF) at age 11 years; one died at age 14 years while awaiting heart transplant and the other underwent left ventricular assist device implantation at the same age. Genetic analysis of one sibling showed a novel frameshift mutation in exon 27 of Duchenne muscular dystrophy (DMD) gene (c.3779_3785delCTTTGGAinsGG), in which seven base pairs are deleted and two are inserted. Although this predicts an amino-acid substitution and premature termination (p.Thr1260Argfs*8), muscle biopsy dystrophin immunostaining instead indicates that the mutation is more likely to alter splicing. Despite relatively preserved skeletal muscular performance, both the siblings developed progressive HF secondary to early-onset DCM. In addition, their 7-year-old nephew with delayed gross motor development, mild proximal muscle weakness and markedly elevated serum creatine kinase level (>13 000 IU l(-1)) at 16 months was recently demonstrated to have the familial DMD mutation. Here, we report a novel genotype of BMD with early-onset DCM and progressive lethal HF during early adolescence.
Details
- Title: Subtitle
- Early-progressive dilated cardiomyopathy in a family with Becker muscular dystrophy related to a novel frameshift mutation in the dystrophin gene exon 27
- Creators
- Takeshi Tsuda - Nemours Cardiac Center, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USAKristi Fitzgerald - Nemours Cardiac Center, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USAMena Scavena - Division of Neurology, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USASamuel Gidding - Nemours Cardiac Center, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USAMary O Cox - Department of Pathology, The University of Iowa, Carver College of Medicine, Iowa City, IA, USAHarold Marks - Division of Neurology, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USAKevin M Flanigan - Nationwide Children's Hospital, Division of Neurology and Center for Gene Therapy, Columbus, OH, USASteven A Moore - Department of Pathology, The University of Iowa, Carver College of Medicine, Iowa City, IA, USA
- Resource Type
- Journal article
- Publication Details
- Journal of human genetics, Vol.60(3), pp.151-155
- Publisher
- England
- DOI
- 10.1038/jhg.2014.112
- PMID
- 25537791
- PMCID
- PMC4374993
- ISSN
- 1434-5161
- eISSN
- 1435-232X
- Grant note
- U54 NS053672 / NINDS NIH HHS 2P20GM103446-12 / NIGMS NIH HHS P20 GM103446 / NIGMS NIH HHS
- Language
- English
- Date published
- 03/2015
- Academic Unit
- Pathology
- Record Identifier
- 9984047667002771
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