title: Somatic mosaicism for Duchenne dystrophy: evidence for genetic normalization mitigating muscle symptoms.
abstract: We describe a young adult male presenting with cardiac failure necessitating cardiac transplantation 7 months after presentation. Skeletal muscle biopsy showed mosaic immunostaining for dystrophin. DNA studies showed somatic mosaicism for a nonsense mutation in the dystrophin gene (Arg2905X). The frequency of normal versus mutant genes were determined in blood/DNA (50:50), muscle/DNA (80:20) and muscle/mRNA (90:10). These data are consistent with genetic normalization processes that may biochemically rescue skeletal muscle in male somatic mosaic patients mitigating muscle symptoms (gradual loss of dystrophin-negative skeletal muscle tissue replaced by dystrophin-positive stem cells). To our knowledge, this is only the second reported case of a clinically ascertained patient showing somatic mosaicism for Duchenne muscular dystrophy (DMD). We hypothesize that many somatic mosaic males for DMD exist, yet they are not detected clinically due to genetic normalization. Somatic mosaicism for DMD should be considered in acute heart failure with dilated cardiomyopathy, as genetic normalization in heart is unlikely to occur.
authors.affiliation: Research Center for Genetic Medicine, Children's National Medical Center, Washington, District of Columbia 20010, USA.
authors.forename: Akanchha
authors.initials: A
authors.lastname: Kesari
authors.forename: Robert
authors.initials: R
authors.lastname: Neel
authors.forename: Lynne
authors.initials: L
authors.lastname: Wagoner
authors.forename: Brennan
authors.initials: B
authors.lastname: Harmon
authors.forename: Christopher
authors.initials: C
authors.lastname: Spurney
authors.forename: Eric P
authors.initials: EP
authors.lastname: Hoffman
mesh_terms: D016189:Dystrophin / Q000235:genetics; D005838:Genotype; D006801:Humans; D033162:Incidental Findings; D008297:Male; D009030:Mosaicism; D018482:Muscle, Skeletal / Q000503:physiopathology*; D020388:Muscular Dystrophy, Duchenne / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D055815:Young Adult
chemical_list: C484258:DMD protein, human; D016189:Dystrophin