title: Analysis of 14 LRRK2 mutations in Parkinson's plus syndromes and late-onset Parkinson's disease.
abstract: The pleomorphic pathology of postmortem LRRK2-positive patients and the frequent association with late-onset Parkinson's disease (LOPD) symptoms suggest that LRRK2 mutations may play a role in Parkinson's Plus disorders and LOPD. Published studies primarily focus on the common G2019S mutation. Analysis of a spectrum of LRRK2 mutations in Parkinson's Plus disorders has yet to be reported. We investigated 14 leucine-rich repeat kinase 2 (LRRK2) mutations in a cohort of Parkinson's Plus disorders and LOPD. A total of 458 patients with progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal ganglionic degeneration (CBGD), atypical Parkinsonism (AP), and LOPD were screened for 14 mutations that span exons 19 to 41 of the LRRK2 gene. Among the LOPD cases, 1 patient was found to harbor the R1441C mutation. He presented with typical features of PD at age of 58 years old and responded well to levodopa. We did not detect any of the 14 mutations in PSP, MSA, CBGD, and AP patients. We highlight the first case of LRRK2 R1441C mutation in late onset sporadic PD of non-European ancestry. Furthermore, extensive mutational screen found LRRK2 mutations to be rare among patients who presented with PSP, MSA, CBGD, and AP.
authors.affiliation: Department of Neurology, Singapore General Hospital, Singapore. gnrtek@sgh.com.sg
authors.forename: E K
authors.initials: EK
authors.lastname: Tan
authors.forename: Lisa
authors.initials: L
authors.lastname: Skipper
authors.forename: Eva
authors.initials: E
authors.lastname: Chua
authors.forename: Meng-Cheong
authors.initials: MC
authors.lastname: Wong
authors.forename: Ratnagopal
authors.initials: R
authors.lastname: Pavanni
authors.forename: Carine
authors.initials: C
authors.lastname: Bonnard
authors.forename: Prasanna
authors.initials: P
authors.lastname: Kolatkar
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Liu
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005820:Genetic Testing; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000175:diagnosis / Q000235:genetics; D010300:Parkinson Disease / Q000175:diagnosis / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000175:diagnosis / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D013132:Spinocerebellar Degenerations / Q000175:diagnosis / Q000235:genetics; D013494:Supranuclear Palsy, Progressive / Q000175:diagnosis / Q000235:genetics
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases