title: Novel valosin containing protein mutation in a Swiss family with hereditary inclusion body myopathy and dementia.
abstract: Inclusion body myopathy associated with Paget's disease of the bone and frontotemporal dementia is a rare but highly penetrant autosomal dominant progressive disorder linked to mutations in valosin containing protein (VCP). Here, we characterize a novel mutation in the linker 1 domain of VCP leading to inclusion body myopathy and/or frontotemporal dementia in 3 generations of a Swiss family. A detailed history of several years of clinical follow-up and electrophysiological, radiological and pathological findings are presented. Five out of 6 individuals suffered from progressive myopathy and 2 out of 6 from frontotemporal dementia, respectively. A radiologically suspected Paget's disease of the bone could not been confirmed at autopsy. This case study illustrates that only a subset of individuals shows the full triad of the disease complex and that clinicopathological findings are - when interpreted apart from familial history - hard to distinguish from sporadic inclusion body myositis.
authors.affiliation: Department of Neurology, University Hospital of Basel, Switzerland; Department of Biomedicine, University Hospital of Basel, Switzerland. peyera@uhbs.ch
authors.forename: Anne-Kathrin
authors.initials: AK
authors.lastname: Peyer
authors.forename: Jochen
authors.initials: J
authors.lastname: Kinter
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hench
authors.forename: Stephan
authors.initials: S
authors.lastname: Frank
authors.forename: Peter
authors.initials: P
authors.lastname: Fuhr
authors.forename: Sandra
authors.initials: S
authors.lastname: Thomann
authors.forename: Arne
authors.initials: A
authors.lastname: Fischmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Kneifel
authors.forename: Pilar
authors.initials: P
authors.lastname: Camaño
authors.forename: Adolfo
authors.initials: A
authors.lastname: López de Munain
authors.forename: Michael
authors.initials: M
authors.lastname: Sinnreich
authors.forename: Susanne
authors.initials: S
authors.lastname: Renaud
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D001706:Biopsy; D018797:Cell Cycle Proteins / Q000235:genetics*; D005260:Female; D057180:Frontotemporal Dementia / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology; D049288:Muscular Dystrophies, Limb-Girdle / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D018979:Myositis, Inclusion Body / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D010001:Osteitis Deformans / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D013557:Switzerland; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein