title: Somatic mosaicism due to a reversion variant causing hemi-atrophy: a novel variant of dystrophinopathy.
abstract: We describe a case of hemi-atrophy in a young adult male, with a positive family history of three maternal uncles with Duchenne muscular dystrophy (DMD). The patient showed progressive weakness localized to the left side, an abnormal electromyography, and creatine kinase levels >3000 IU/l. Muscle biopsy showed both dystrophin-positive and -negative myofibers. An out-of-frame duplication variant in DMD, that is, c.(93+1_94-1)_(649+1_650-1)dup(p.?) resulting in duplication of exons 3-7 was inherited, but the muscle biopsy showed dystrophin mRNA with and without the duplication. Dystrophin quantification using mass spectrometry showed 25% normal dystrophin protein levels in the muscle biopsy from the stronger right side. Sex chromosome aneuploidy was ruled out. We conclude that the patient inherited the duplication variant, but early in development an inner cell mass underwent a somatic recombination event removing the duplication and restoring dystrophin expression. To our knowledge, this is the first report of a reversion leading to somatic mosaicism in DMD.
authors.affiliation: Department of Integrative Systems Biology, The George Washington University School of Medicine, Washington, DC, USA.|Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA.
authors.forename: Jaya
authors.initials: J
authors.lastname: Punetha
authors.affiliation: Department of Neurology, The University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Simin
authors.initials: S
authors.lastname: Mansoor
authors.affiliation: Department of Neurology, The University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Tulio E
authors.initials: TE
authors.lastname: Bertorini
authors.affiliation: Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA.
authors.forename: Akanchha
authors.initials: A
authors.lastname: Kesari
authors.affiliation: Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA.
authors.forename: Kristy J
authors.initials: KJ
authors.lastname: Brown
authors.affiliation: Department of Integrative Systems Biology, The George Washington University School of Medicine, Washington, DC, USA.|Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Hoffman
mesh_terms: D003402:Creatine Kinase / Q000097:blood; D016189:Dystrophin / Q000235:genetics; D005091:Exons; D020440:Gene Duplication; D006801:Humans; D008297:Male; D009030:Mosaicism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000175:diagnosis / Q000235:genetics*; D011995:Recombination, Genetic; D055815:Young Adult
chemical_list: D016189:Dystrophin; D003402:Creatine Kinase