Abstract
Mutations in the leucine rich repeat kinase 2 (LRRK2) gene are among the most common genetic causes of Lewy body Parkinson's disease (PD). However, LRRK2 mutations can also lead to a variety of pathological phenotypes other than typical PD, including relatively pure nigrostriatal cell loss without alpha-synuclein-positive Lewy bodies or Lewy neurites, progressive supranuclear palsy (PSP), and multiple system atrophy (MSA). The mechanisms behind this remarkable pleomorphic pathology are currently unclear. To genetically and pathologically characterize a case with a LRRK2, p.Ile1371Val rare variant and pathologically proven MSA. From the brain donation program at the Parkinson's Institute and Clinical Center, we selected 26 brains with family history and a with clinicopathological diagnosis of PD (n = 20), MSA (n = 4), or PSP (n = 2). We performed neuropathological evaluation, including alpha-synuclein and tau immunohistochemistry and sequenced 188 genes that have been reported as causative for or associated with neurodegenerative diseases. We identified a known LRRK2, p.Ile1371Val genetic variant in a case with clinically diagnosed and pathologically proven MSA. Neuropathology revealed that the olivopontocerebellar system was mo...Continue Reading
References
Jan 29, 2000·Acta Neuropathologica·K WakabayashiH Takahashi
Jun 27, 2000·Acta Neuropathologica·K Gwinn-HardyD W Dickson
Oct 23, 2001·Neuropathology : Official Journal of the Japanese Society of Neuropathology·T YokoyamaS Yagishita
May 12, 2004·Neurology·Z K WszolekD W Dickson
Nov 16, 2004·Neuron·Alexander ZimprichThomas Gasser
Sep 15, 2005·Neurology·C Paisán-RuízE Rogaeva
Dec 8, 2005·European Journal of Human Genetics : EJHG·Alessio Di FonzoUNKNOWN Italian Parkinson's Genetics Network
Apr 15, 2006·Neuron Glia Biology·David W MillerDennis W Dickson
Oct 25, 2006·Neurology·A RajputM J Farrer
Dec 7, 2006·Movement Disorders : Official Journal of the Movement Disorder Society·Maria Teresa GiordanaVincenzo Bonifati
Sep 23, 2008·Parkinsonism & Related Disorders·Kazuko HasegawaSaburo Yagishita
Apr 10, 2009·Journal of Medical Genetics·S LesageUNKNOWN French Parkinson's Disease Genetics Study Group
Jul 21, 2010·The Biochemical Journal·R Jeremy NicholsDario R Alessi
Aug 20, 2010·Movement Disorders : Official Journal of the Movement Disorder Society·Barbara Jasinska-MygaMatthew J Farrer
Jul 29, 2011·Journal of Human Genetics·Naomi SekiShoji Tsuji
Sep 3, 2011·Lancet Neurology·Owen A RossUNKNOWN Genetic Epidemiology Of Parkinson's Disease (GEO-PD) Consortium
May 5, 2012·Acta Neuropathologica·Claudio RuffmannGiorgio Giaccone
Nov 18, 2014·JAMA Neurology·Lorraine V KaliaConnie Marras
Apr 23, 2015·Journal of the Neurological Sciences·Milena Z JankovićVladimir S Kostić
Dec 2, 2015·Nature Genetics·J William LangstonCarrolee Barlow
Citations
May 12, 2019·Movement Disorders : Official Journal of the Movement Disorder Society·Giulietta Maria RiboldiSteven Frucht
Apr 23, 2020·Movement Disorders : Official Journal of the Movement Disorder Society·Stuart J McCarterWolfgang Singer
Jan 27, 2021·International Journal of Molecular Sciences·Vinita G Chittoor-VinodBirgitt Schüle
Nov 19, 2020·Movement Disorders : Official Journal of the Movement Disorder Society·Oihana Errea, Maria Cruz Rodriguez-Oroz
Nov 24, 2020·Frontiers in Neurology·Peggy S EisBirgitt Schüle
Feb 6, 2021·Neurología : publicación oficial de la Sociedad Española de Neurología·G Fernández-PajarínA Castro
Jul 14, 2021·Expert Review of Neurotherapeutics·Luca MarsiliCarlo Colosimo
Oct 7, 2021·Journal of Neural Transmission·David J MarmionJeffrey H Kordower