title: Deletion of exons 3-9 encompassing a mutational hot spot in the DMD gene presents an asymptomatic phenotype, indicating a target region for multiexon skipping therapy.
abstract: Few cases of dystrophinopathy show an asymptomatic phenotype with mutations in the 5' (exons 3-7) hot spot in the Duchenne muscular dystrophy (DMD) gene. Our patient showed increased serum creatine kinase levels at 12 years of age. A muscle biopsy at 15 years of age led to a diagnosis of Becker muscular dystrophy. The patient showed a slight decrease in cardiac function at the age of 21 years and was administered a β-blocker, but there was no muscle involvement even at the age of 27 years. A deletion of exons 3-9 encompassing a mutational hot spot in the DMD gene was detected, and dystrophin protein expression was ∼15% that of control level. We propose that in-frame deletion of exons 3-9 may produce a functional protein, and that multiexon skipping therapy targeting these exons may be feasible for severe dystrophic patients with a mutation in the 5' hot spot of the DMD gene.
authors.affiliation: Intractable Disease Care Center, Shinshu University Hospital, Matsumoto, Japan.|Department of Neurology and Rheumatology, Shinshu University Hospital, Matsumoto, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Nakamura
authors.affiliation: Division of Rehabilitation, Nagano Children's Hospital, Azumino, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Fueki
authors.affiliation: Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Shiba
authors.affiliation: Department of Cardiovascular Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Motoki
authors.affiliation: Intractable Disease Care Center, Shinshu University Hospital, Matsumoto, Japan.|Department of Neurology and Rheumatology, Shinshu University Hospital, Matsumoto, Japan.
authors.forename: Daigo
authors.initials: D
authors.lastname: Miyazaki
authors.affiliation: School of Health Science, Shinshu University, Matsumoto, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Nishizawa
authors.affiliation: Department of Medical Genetics, School of Human Development, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Echigoya
authors.affiliation: Department of Medical Genetics, School of Human Development, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Yokota
authors.affiliation: Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Aoki
authors.affiliation: Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Shin'ichi
authors.initials: S
authors.lastname: Takeda
mesh_terms: D000328:Adult; D058070:Asymptomatic Diseases; D001706:Biopsy; D016189:Dystrophin / Q000235:genetics*; D005091:Exons; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D009154:Mutation; D010641:Phenotype; D017422:Sequence Analysis, DNA; D014057:Tomography, X-Ray Computed
chemical_list: D016189:Dystrophin