Corticobasal syndrome and primary progressive aphasia as manifestations of <i>LRRK2</i> gene mutations

Abstract

<b>Background: </b> Mutations in the <i>LRRK2</i> gene are an important cause of familial and nonfamilial parkinsonism. Despite pleomorphic pathology, <i>LRRK2</i> mutations are believed to manifest clinically as typical Parkinson disease (PD). However, most genetic screens have been limited to PD clinic populations. <b>Objective: </b> To clinically characterize <i>LRRK2</i> mutations in cases recruited from a spectrum of neurodegenerative diseases. <b>Methods: </b> We screened for the common G2019S mutation and several additional previously reported <i>LRRK2</i> mutations in 434 individuals. A total of 254 patients recruited from neurodegenerative disease clinics and 180 neurodegenerative disease autopsy cases from the University of Pennsylvania brain bank were evaluated. <b>Results: </b> Eight cases were found to harbor a <i>LRRK2</i> mutation. Among patients with a mutation, two presented with cognitive deficits leading to clinical diagnoses of corticobasal syndrome and primary progressive aphasia. <b>Conclusion: </b> The clinical presentation of <i>LRRK2</i>-associated neurodegenerative disease may be more heterogeneous than previously assumed. <b>GLOSSARY: </b><b>AD</b> = Alzheimer disease; <b>ALS</b> = amyotrophic lateral sclerosis; <b>CBD</b> = corticobasal degeneration; <b>CBS</b> = corticobasal syndrome; <b>CDNR</b> = Center for Neurodegenerative Disease Research; <b>DLB</b> = dementia with Lewy bodies; <b>EPS</b> = extrapyramidal symptoms; <b>FTD</b> = frontotemporal dementia; <b>FTLD</b> = frontotemporal lobar degeneration; <b>FWHM</b> = full width at half maximum; <b>LBVAD</b> = Lewy body variant of AD; <b>PD</b> = Parkinson disease; <b>PPA</b> = primary progressive aphasia; <b>PSP</b> = progressive supranuclear palsy; <b>UPenn</b> = University of Pennsylvania; <b>UCSF</b> = University of California San Francisco.