DNM3 and genetic modifiers of age of onset in LRRK2 Gly2019Ser parkinsonism: a genome-wide linkage and association study

Publication date: Available online 28 September 2016 Source:The Lancet Neurology Author(s): Joanne Trinh, Emil K Gustavsson, Carles Vilariño-Güell, Stephanie Bortnick, Jeanne Latourelle, Marna B McKenzie, Chelsea Szu Tu, Ekaterina Nosova, Jaskaran Khinda, Austen Milnerwood, Suzanne Lesage, Alexis Brice, Meriem Tazir, Jan O Aasly, Laura Parkkinen, Hazal Haytural, Tatiana Foroud, Richard H Myers, Samia Ben Sassi, Emna Hentati, Fatma Nabli, Emna Farhat, Rim Amouri, Fayçal Hentati, Matthew J Farrer Background Leucine-rich repeat kinase 2 (LRRK2) mutation 6055G→A (Gly2019Ser) accounts for roughly 1% of patients with Parkinson's disease in white populations, 13–30% in Ashkenazi Jewish populations, and 30–40% in North African Arab-Berber populations, although age of onset is variable. Some carriers have early-onset parkinsonism, whereas others remain asymptomatic despite advanced age. We aimed to use a genome-wide approach to identify genetic variability that directly affects LRRK2 Gly2019Ser penetrance. Methods Between 2006 and 2012, we recruited Arab-Berber patients with Parkinson's disease and their family members (aged 18 years or older) at the Mongi Ben Hamida National Institute of Neurology (Tunis, Tunisia). Patients with Parkinson's disease were diagnosed by movement disorder specialists in accordance with the UK Parkinson's Disease Society Brain Bank criteria, without exclusion of familial parkinsonism. LRRK2 carrier status was confirmed ...
Source: The Lancet Neurology - Category: Neurology Source Type: research