Early-progressive dilated cardiomyopathy in a family with Becker muscular dystrophy related to a novel frameshift mutation in the dystrophin gene exon 27.
J Hum Genet
; 60(3): 151-5, 2015 Mar.
Article
em En
| MEDLINE
| ID: mdl-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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cardiomiopatia Dilatada
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Éxons
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Distrofina
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Mutação da Fase de Leitura
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Distrofia Muscular de Duchenne
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
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Child
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Female
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Humans
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Male
Idioma:
En
Revista:
J Hum Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos