title: Nuclear inclusions mimicking poly(A)-binding protein nuclear 1 inclusions in a case of inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia with a novel mutation in the valosin-containing protein gene.
abstract: A middle-aged Japanese man presented with slowly progressive asymmetric weakness of legs and arm but had neither ptosis nor dysphagia. He had a family history of similar condition suggestive of autosomal dominant inheritance. A muscle biopsy showed mixture of neurogenic atrophy and myopathy with rimmed vacuoles. Furthermore we found intranuclear inclusions that had a fine structure mimicking that of inclusions reported in oculopharyngeal muscular dystrophy (OPMD). Immunohistochemical staining for polyadenylate-binding nuclear protein 1, which is identified within the nuclear inclusions of OPMD, demonstrated nuclear positivity in this case. However, OPMD was thought unlikely based on the clinical features and results of genetic analyses. Instead, a novel mutation in valosin-containing protein, c.376A>T (p.Ile126Phe), was revealed. A diagnosis of inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia was made. This is the first report of polyadenylate-binding nuclear protein 1-positive nuclear inclusions in the muscle of this condition.
authors.affiliation: Department of Neurology, Tokyo Metropolitan Neurological Hospital, 2-6-1 Musashidai, Fuchu, Tokyo 183-0042, Japan. Electronic address: mtbrs@nifty.com.
authors.forename: Shiro
authors.initials: S
authors.lastname: Matsubara
authors.affiliation: Department of Neurology, Tokyo Metropolitan Neurological Hospital, 2-6-1 Musashidai, Fuchu, Tokyo 183-0042, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Neuropathology, Tokyo Metropolitan Neurological Hospital, 2-6-1 Musashidai, Fuchu, Tokyo 183-0042, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Komori
authors.affiliation: Department of Neurology, National Center Hospital.
authors.forename: Madoka
authors.initials: M
authors.lastname: Mori-Yoshimura
authors.affiliation: National Center Hospital, National Center of Neurology and Psychiatry, 4-4-1 Ogawahigashi, Kodaira, Tokyo 187-8551, Japan; Medical Genome Center, National Center of Neurology and Psychiatry, 4-4-1 Ogawahigashi, Kodaira, Tokyo 187-8551, Japan; National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-4-1 Ogawahigashi, Kodaira, Tokyo 187-8551, Japan.
authors.forename: Narihiro
authors.initials: N
authors.lastname: Minami
authors.affiliation: Department of Pathophysiology, Tokyo Medical University, 6-1-1 Shinjyuku, Shinjyuku-ku, Tokyo 160-0022, Japan.
authors.forename: Yukiko K
authors.initials: YK
authors.lastname: Hayashi
mesh_terms: D057180:Frontotemporal Dementia / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009154:Mutation; D018979:Myositis, Inclusion Body / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010001:Osteitis Deformans / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D039122:Poly(A)-Binding Protein I / Q000378:metabolism; D000074405:Valosin Containing Protein / Q000235:genetics*
chemical_list: C576588:PABPN1 protein, human; D039122:Poly(A)-Binding Protein I; C000614178:VCP protein, human; D000074405:Valosin Containing Protein
keywords: IBMPFD; Oculopharyngeal muscular dystrophy; Poly(A)-binding protein nuclear 1; Valosin-containing protein