title: Lrrk2 G2019S substitution in frontotemporal lobar degeneration with ubiquitin-immunoreactive neuronal inclusions.
abstract: Leucine-rich repeat kinase 2 (LRRK2) mutation carriers can develop clinical symptoms other than typical parkinsonism such as dementia, amyotrophy or dystonia. To determine if LRRK2 mutations might be involved in frontotemporal dementia (FTD), 5 individuals with multiplex familial FTD kindreds and 41 pathologically confirmed cases of FTD, including 23 with a family history of dementia, were screened for genetic variations in the LRRK2 gene. We identified a LRRK2 mutation leading to the G2019S amino acid substitution in a 79-year-old woman with frontotemporal lobar degeneration with ubiquitinated neuronal intranuclear inclusions (FTLD-U/NII) and a possible family history of tremor. These findings may be coincidental; however, there is a small nucleus of LRRK2-positive patients displaying atypical features suggesting a role for this protein in other neurodegenerative disorders.
authors.affiliation: Department of Neuroscience, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
authors.forename: Justus C
authors.initials: JC
authors.lastname: Dächsel
authors.forename: Owen A
authors.initials: OA
authors.lastname: Ross
authors.forename: Ignacio F
authors.initials: IF
authors.lastname: Mata
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kachergus
authors.forename: Mathias
authors.initials: M
authors.lastname: Toft
authors.forename: Ashley
authors.initials: A
authors.lastname: Cannon
authors.forename: Matt
authors.initials: M
authors.lastname: Baker
authors.forename: Jennifer
authors.initials: J
authors.lastname: Adamson
authors.forename: Mike
authors.initials: M
authors.lastname: Hutton
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Farrer
mesh_terms: D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics*; D003704:Dementia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D005998:Glycine / Q000235:genetics; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism*; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012694:Serine / Q000235:genetics; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D025801:Ubiquitin; D012694:Serine; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D005998:Glycine