Neuroscience Letters 389 (2005) 137–139 The dardarin G2019S mutation is a common cause of Parkinson’s disease but not other neurodegenerative diseases Dena Hernandez a , Coro Paisan Ruiz a , Anthony Crawley a , Roneil Malkani a , John Werner a , Katrina Gwinn-Hardy a , Dennis Dickson b , Fabienne Wavrant DeVrieze a , John Hardy a,∗ , Andrew Singleton a a Laboratory of Neurogenetics, National Institutes on Aging and of Neurological Diseases and Stroke, Porter Neuroscience Building, Building 10, Room 6C103, 35, Convent Drive, Bethesda, MD 20892, USA b Birdsall Building, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA Received 28 June 2005; received in revised form 19 July 2005; accepted 20 July 2005 Abstract Mutations in the leucine-rich kinase 2 gene (LRRK2) encoding dardarin, on chromosome 12, are a common cause of familial and sporadic Parkinson’s disease. The most common mutation, a heterozygous 6055G > A transition (G2019S) accounts for approximately 3–10% of familial Parkinson’s disease and 1–8% sporadic Parkinson’s disease in several European-derived populations. Some families with disease caused by LRRK2 mutations have been reported to include patients with highly variable clinical and pathological features. We screened for the most common LRRK2 mutation in a series of patients with Parkinson’s Disease, Alzheimer’s disease, Progressive Supranuclear Palsy, Multiple System Atrophy and frontotemporal dementia, as well as in neurologically normal controls. The mutation was found only in Parkinson’s disease patients or their relatives and not in those with other neurodegenerative disease. © 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Parkinson’s disease; Parkinsonism; Dementia; LRRK2; Dardarin genetics Parkinson’s disease is a common neurodegenerative disorder, affecting 3% of those >75 years of age [3]. It is associated with resting tremor, postural rigidity and bradykinesia. The neuropathologic hallmarks of Parkinson’s disease are loss of dopaminergic neurons and deposition of cytoplasmic aggre- gates termed Lewy bodies, which contain -synuclein and ubiquitin, especially in the substantia nigra. Genetic analysis has implicated several genes in parkinso- nian syndromes [7]. Most recently, mutations in the LRRK2 gene were reported [15]. These mutations occurred in several families whose clinical features were usually of Parkinson’s disease [8,16,17,19]. However, some families show neu- ropathological heterogeneity with some affected individuals exhibiting Lewy bodies, in association with neuronal loss and gliosis in the substantia nigra [6] and others having either tau pathology and resembling progressive supranuclear palsy and ∗ Corresponding author. Tel.: +1 301 451 3829; fax: +1 301 480 0335. E-mail address: hardyj@mail.nih.gov (J. Hardy). Table 1 Number of cases screened for the G2019S dardarin mutation Diagnosis G2019S screened Parkinson’s disease 719 Late onset Alzheimer’s disease 1444 Progressive Supranuclear Palsy 186 Essential tremor 18 Restless leg syndrome 94 Frontal temporal dementia and CBGD/tauopathy 40 Dystonia 17 Controls 2680 CBGD: cortical-basal ganglionic degeneration. still others lacking distinctive histopathology; these patholo- gies occurred in the context of variable clinical phenotypes [5,19]. This variety of clinical and pathological features asso- ciated with patients possessing LRRK2 mutations suggests that they can lead to the central pathogenic event of nigral degeneration, and produce parkinsonian phenotypes, along with variable pathological features [19]. Furthermore, the 0304-3940/$ – see front matter © 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2005.07.044