title: Early-progressive dilated cardiomyopathy in a family with Becker muscular dystrophy related to a novel frameshift mutation in the dystrophin gene exon 27.
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.
authors.affiliation: Nemours Cardiac Center, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tsuda
authors.affiliation: Nemours Cardiac Center, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA.
authors.forename: Kristi
authors.initials: K
authors.lastname: Fitzgerald
authors.affiliation: Division of Neurology, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA.
authors.forename: Mena
authors.initials: M
authors.lastname: Scavena
authors.affiliation: Nemours Cardiac Center, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Gidding
authors.affiliation: Department of Pathology, The University of Iowa, Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Mary O
authors.initials: MO
authors.lastname: Cox
authors.affiliation: Division of Neurology, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA.
authors.forename: Harold
authors.initials: H
authors.lastname: Marks
authors.affiliation: Nationwide Children's Hospital, Division of Neurology and Center for Gene Therapy, Columbus, OH, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Flanigan
authors.affiliation: Department of Pathology, The University of Iowa, Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Moore
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D015153:Blotting, Western; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002648:Child; D004252:DNA Mutational Analysis; D018450:Disease Progression; D016189:Dystrophin / Q000235:genetics* / Q000378:metabolism; D005091:Exons / Q000235:genetics*; D005192:Family Health; D017809:Fatal Outcome; D005260:Female; D016368:Frameshift Mutation; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010375:Pedigree; D035781:Siblings; D013997:Time Factors
chemical_list: D016189:Dystrophin