title: Voxel-based morphometry in frontotemporal lobar degeneration with ubiquitin-positive inclusions with and without progranulin mutations.
abstract: BACKGROUND
  Mutations in the progranulin gene (PGRN) have recently been identified as a cause of frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) in some families.
  
  
  OBJECTIVE
  To determine whether there is a difference in the patterns of atrophy in FTLD-U cases with and without PGRN mutations.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  Brain bank of a tertiary care medical center. Patients Eight subjects who had screened positive for PGRN mutations (PGRN-positive) and who underwent volumetric magnetic resonance imaging were identified. Subjects were then matched by clinical diagnosis to a group of 8 subjects with a pathological diagnosis of FTLD-U who had screened negative for PGRN mutations (PGRN-negative). All subjects were then age-matched and sex-matched to a control subject.
  
  
  METHODS
  Voxel-based morphometry was used to assess the patterns of gray matter atrophy in the PGRN-positive group compared with the PGRN-negative group and compared with controls.
  
  
  RESULTS
  The PGRN-positive group showed a widespread and severe pattern of gray matter loss predominantly affecting the frontal, temporal, and parietal lobes. The PGRN-negative group showed a less severe pattern of gray matter loss restricted mainly to the temporal and frontal lobes. On direct comparison, the PGRN-positive group showed greater gray matter loss in the frontal and parietal lobes compared with the PGRN-negative group.
  
  
  CONCLUSIONS
  Findings from this study suggest that PGRN mutations may be associated with a specific and severe pattern of cerebral atrophy in subjects with FTLD-U.
authors.affiliation: Division of Behavioral Neurology, Department of Neurology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Whitwell
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.forename: Matthew
authors.initials: M
authors.lastname: Baker
authors.forename: Rosa
authors.initials: R
authors.lastname: Rademakers
authors.forename: Jennifer
authors.initials: J
authors.lastname: Adamson
authors.forename: Bradley F
authors.initials: BF
authors.lastname: Boeve
authors.forename: David S
authors.initials: DS
authors.lastname: Knopman
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Parisi
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
authors.forename: Michael L
authors.initials: ML
authors.lastname: Hutton
authors.forename: Keith A
authors.initials: KA
authors.lastname: Josephs
mesh_terms: D000368:Aged; D001931:Brain Mapping; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology*; D003704:Dementia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000077153:Progranulins; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D025801:Ubiquitin