Isolated cardiomyopathy caused by a DMD nonsense mutation in somatic mosaicism: genetic normalization in skeletal muscle
Por:
Juan-Mateu, J, Paradas, C, Olive, M, Verdura, E, Rivas, E, Gonzalez-Quereda, L, Rodriguez, MJ, Baiget, M, Gallano, P
Publicada:
1 dic 2012
Resumen:
X-linked dilated cardiomyopathy is a pure cardiac dystrophinopathy phenotype mainly caused by DMD mutations that present a specific transcription effect in cardiac tissue. We report a 26-year-old male who presented with severe dilated cardiomyopathy and high creatine kinase. The patient did not complain of skeletal muscle weakness. A muscle biopsy showed mild dystrophic changes and a low proportion of dystrophin-negative fibres. A molecular study identified a nonsense DMD mutation (p.Arg2098X) in somatic mosaicism. The ratio of mutant versus normal allele in blood and skeletal muscle suggests selective pressure against mutant muscle cells, a process known as genetic normalization. We hypothesize that this process may have mitigated skeletal muscle symptoms in this patient. This is the second report of a DMD somatic mosaic with evidence of genetic normalization in muscle. Somatic DMD mutations should be considered in patients presenting with idiopathic dilated cardiomyopathy.
Filiaciones:
Juan-Mateu, J:
Hosp Santa Creu & Sant Pau, Dept Genet, CIBERER, Barcelona 08025, Spain
Univ Barcelona, Barcelona, Spain
Paradas, C:
Hosp Virgen del Rocio IBiS CIBERNED, Dept Neurol, Seville, Spain
Olive, M:
Hosp Llobregat, CIBERNED, IDIBELL Hosp Bellvitge, Inst Neuropatol, Lhospitalet De Llobregat, Spain
Verdura, E:
Hosp Santa Creu & Sant Pau, Dept Genet, CIBERER, Barcelona 08025, Spain
Rivas, E:
Hosp Virgen del Rocio, Dept Pathol, Seville, Spain
Gonzalez-Quereda, L:
Hosp Santa Creu & Sant Pau, Dept Genet, CIBERER, Barcelona 08025, Spain
Rodriguez, MJ:
Hosp Santa Creu & Sant Pau, Dept Genet, CIBERER, Barcelona 08025, Spain
Baiget, M:
Hosp Santa Creu & Sant Pau, Dept Genet, CIBERER, Barcelona 08025, Spain
Gallano, P:
Hosp Santa Creu & Sant Pau, Dept Genet, CIBERER, Barcelona 08025, Spain
|