title: Isolated cardiomyopathy caused by a DMD nonsense mutation in somatic mosaicism: genetic normalization in skeletal muscle.
abstract: 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.
authors.affiliation: Genetics Department, Hospital Sant Pau, CIBERER, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Juan-Mateu
authors.forename: C
authors.initials: C
authors.lastname: Paradas
authors.forename: M
authors.initials: M
authors.lastname: Olivé
authors.forename: E
authors.initials: E
authors.lastname: Verdura
authors.forename: E
authors.initials: E
authors.lastname: Rivas
authors.forename: L
authors.initials: L
authors.lastname: González-Quereda
authors.forename: M J
authors.initials: MJ
authors.lastname: Rodríguez
authors.forename: M
authors.initials: M
authors.lastname: Baiget
authors.forename: P
authors.initials: P
authors.lastname: Gallano
mesh_terms: D000328:Adult; D015153:Blotting, Western; D002311:Cardiomyopathy, Dilated / Q000235:genetics*; D018389:Codon, Nonsense / Q000235:genetics*; D003402:Creatine Kinase / Q000097:blood; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D016189:Dystrophin / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D009030:Mosaicism; D018482:Muscle, Skeletal; D012641:Selection, Genetic
chemical_list: D018389:Codon, Nonsense; C484258:DMD protein, human; D017931:DNA Primers; D016189:Dystrophin; D003402:Creatine Kinase