title: Spinocerebellar ataxia type 7 (SCA7): a neurodegenerative disorder with neuronal intranuclear inclusions.
abstract: Autosomal dominant cerebellar ataxia with progressive macular degeneration is caused by a CAG/glutamine repeat expansion in the SCA7 gene/protein. Neuronal intranuclear inclusions were detected in the brain of an early onset SCA7 case with the 1C2 antibody directed against an expanded polyglutamine domain. Nuclear inclusions were most frequent in the inferior olivary complex, a site of severe neuronal loss in SCA7. They were also observed in other brain regions, including the cerebral cortex, not considered to be affected in the disease. Using confocal microscopy we showed that some inclusions were ubiquitinated, but to varying degrees, ranging from <1% in the cerebral cortex to 60% in the inferior olive. In addition, we also observed cytoplasmic staining using the 1C2 antibody, particularly in the supramarginal gyrus, the hippocampus, the thalamus, the lateral geniculate body and the pontine nuclei. These data confirm that the presence of intranuclear inclusions in neurons is a common characteristic of disorders caused by CAG/polyglutamine expansions, but unlike what has been reported for Huntington's disease, SCA1 and SCA3/MJD, in SCA7 the inclusions were not restricted to the sites of severe neuronal loss.
authors.affiliation: INSERM U289, Laboratoire de Neuropathologie R.Escourolle, Fédération de Neurologie, 47 boulevard de l'Hôpital, 75651 Paris Cedex 13, France.
authors.forename: M
authors.initials: M
authors.lastname: Holmberg
authors.forename: C
authors.initials: C
authors.lastname: Duyckaerts
authors.forename: A
authors.initials: A
authors.lastname: Dürr
authors.forename: G
authors.initials: G
authors.lastname: Cancel
authors.forename: I
authors.initials: I
authors.lastname: Gourfinkel-An
authors.forename: P
authors.initials: P
authors.lastname: Damier
authors.forename: B
authors.initials: B
authors.lastname: Faucheux
authors.forename: Y
authors.initials: Y
authors.lastname: Trottier
authors.forename: E C
authors.initials: EC
authors.lastname: Hirsch
authors.forename: Y
authors.initials: Y
authors.lastname: Agid
authors.forename: A
authors.initials: A
authors.lastname: Brice
mesh_terms: D000067719:Ataxin-7; D001921:Brain / Q000473:pathology; D002467:Cell Nucleus / Q000737:chemistry / Q000473:pathology*; D002648:Child; D005973:Glutamine / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000737:chemistry / Q000473:pathology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000737:chemistry / Q000473:pathology; D009479:Neuropeptides / Q000032:analysis; D009687:Nuclear Proteins / Q000032:analysis; D013132:Spinocerebellar Degenerations / Q000473:pathology*
chemical_list: C490341:ANP32B protein, human; C000593829:ATXN7 protein, human; D000067719:Ataxin-7; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D009687:Nuclear Proteins; D005973:Glutamine