Summary
The etiology for Parkinson’s disease (PD) remains unknown. Genetic causes have been identified with several distinct mutations. Recently, 9 mutations involving a novel gene, leucine-rich repeat kinase 2 (LRRK2), have been identified as the cause of autosomal dominant PD in kindreds, with some of them previously linked to the PARK8 locus on chromosome 12. LRRK2 mutations are relatively common genetic causes of familial and sporadic PD. In addition, these mutations have been identified in diverse populations. The clinical and pathologic features of LRRK2-associated PD are indistinguishable from idiopathic PD; however, considerable clinical and pathologic variability exists even among kindreds. This short review highlights the clinical and pathologic features in LRRK2-associated parkinsonism.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Adams JR, van Netten H, Schultzer M, Mak E, Mckenzie J, Strongosky A, Sossi V, Ruth TJ, Lee CS, Farrer M, Gasser T, Uitti RJ, Calne DB, Wszolek ZK, Stoessl AJ (2005) PET in LRRK2 mutations: comparison to sporadic Parkinson’s disease and evidence for presymptomatic compensation. Brain 128: 2777–2785
Di Fonzo A, Rohe CF, Ferreira J, Chien HF, Vacca L, Stocchi F, Guedes L, Fabrizio E, Manfredi M, Vanacore N, Goldwurm S, Breedveld G, Sampaio C, Meco G, Barbosa E, Oostra BA, Bonifati V, Italian Parkinson Genetics Network (2005) A frequent LRRK2 gene mutation associated with autosomal dominant Parkinson’s disease. Lancet 365: 412–415
Eriksen JL, Wszolek Z, Petrucelli L (2005) Molecular pathogenesis of Parkinson disease. Arch Neurol 62: 353–357
Funayama M, Hasegawa K, Kowa H, Saito M, Tsuji S, Obata F (2002) A new locus for Parkinson’s disease (PARK8) maps to chromosome 12p11.2–q13.1. Ann Neurol 51: 296–301
Funayama M, Hasegawa K, Ohta E, Kawashima N, Komiyama M, Kowa H, Tsuji S, Obata F (2005) An LRRK2 mutation as a cause for the parkinsonism in the original PARK8 family. Ann Neurol 57: 918–921
Gilks WP, Abou-Sleiman PM, Gandhi S, Jain S, Singleton A, Lees AJ, Shaw K, Bhatia KP, Bonifati V, Quinn NP, Lynch J, Healy DG, Holton JL, Revesz T, Wood NW (2005) A common LRRK2 mutation in idiopathic Parkinson’s disease. Lancet 365: 415–416
Hernandez DG, Paisan-Ruiz C, McInerney-Leo A, Jain S, Meyer-Lindenberg A, Evans EW, Berman KF, Johnson J, Auburger G, Schaffer AA, Lopez GJ, Nussbaum RL, Singleton AB (2005) Clinical and positron emission tomography of Parkinson’s disease caused by LRRK2. Ann Neurol 57: 453–456
Kachergus J, Mata IF, Hulihan M, Taylor JP, Lincoln S, Aasly J, Gibson JM, Ross OA, Lynch T, Wiley J, Payami H, Nutt J, Maraganore DM, Czyzewski K, Styczynska M, Wszolek ZK, Farrer MJ, Toft M (2005) Identification of a novel LRRK2 mutation linked to autosomal dominant parkinsonism: evidence of a common founder across European populations. Am J Hum Genet 76: 672–680
Nichols WC, Pankratz N, Hernandez D, Paisan-Ruiz C, Jain S, Halter CA, Michaels VE, Reed T, Rudolph A, Shults CW, Singleton A, Foroud T, Parkinson Study Group-PROGENI investigators (2005) Genetic screening for a single common LRRK2 mutation in familiar Parkinson’s disease. Lancet 365: 410–412
Paisan-Ruiz C, Jain S, Evans EW, Gilks WP, Simon J, van der Brug M, Lopez de Munain A, Aparicio S, Gil AM, Khan N, Johnson J, Martinez NJ, Nicholl D, Carrera IM, Pena AS, de Silva R, Lees A, Marti-Masso JF, Perez-Tur J, Wood NW, Singleton AB (2004) Cloning of the gene containing mutations that cause PARK8-linked Parkinson’s disease. Neuron 44: 595–600
Paisan-Ruiz C, Saenz A, Lopez de Munain A, Marti I, Martinez Gil A, Marti-Masso JF, Perez-Tur J (2005) Familial Parkinson’s disease: clinical and genetic analysis of four Basque families. Ann Neurol 57: 365–372
Ross O, Dickson D, Farrer M (2005) Neuropathology of familial Parkinson’s disease to LRRK2 G20 19S mutation [abstract]. Parkinsonism Relat Disord 11[Suppl 2]: 253
Wszolek ZK, Pfeiffer B, Fulgham JR, Parisi JE, Thompson BM, Uitti RJ, Calne DB, Pfeiffer RF (1995) Western Nebraska family (family D) with autosomal dominant parkinsonism. Neurology 45: 502–505
Wszolek ZK, Pfeiffer RF, Tsuboi Y, Uitti RJ, McComb RD, Stoessl AJ, Strongosky AJ, Zimprich A, Muller-Myhsok B, Farrer MJ, Gasser T, Calne DB, Dickson DW (2004) Autosomal dominant parkinsonism associated with variable synuclein and tau pathology. Neurology 62: 1619–1622
Wszolek ZK, Vieregge P, Uitti RJ, Gasser T, Yasuhara O, Mcgeer P, Berry K, Calne DB, Vingerhoets FJG, Klein C, Pfeiffer RF (1997) German-Canadian family (family A) with parkinsonism, amyotrophy, and dementia: longitudinal observations. Parkinsonism Relat Disord 3: 125–173
Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, Kachergus J, Hulihan M, Uitti RJ, Calne DB, Stoessl AJ, Pfeiffer RF, Patenge N, Carbajal IC, Vieregge P, Asmus F, Muller-Myhsok B, Dickson DW, Meitinger T, Strom TM, Wszolek ZK, Gasser T (2004a) Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44: 601–607
Zimprich A, Muller-Myhsok B, Farrer M, Leitner P, Sharma M, Hulihan M, Lockhart P, Strongosky A, Kachergus J, Calne DB, Stoessl J, Uitti RJ, Pfeiffer RF, Trenkwalder C, Homann N, Ott E, Wenzel K, Asmus F, Hardy J, Wszolek Z, Gasser T (2004b) The PARK8 locus in autosomal dominant parkinsonism: confirmation of linkage and further delineation of the disease-containing interval. Am J Hum Genet 74: 11–19 (Erratum in: Am J Hum Genet 75: 534)
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2006 Springer-Verlag
About this paper
Cite this paper
Whaley, N.R., Uitti, R.J., Dickson, D.W., Farrer, M.J., Wszolek, Z.K. (2006). Clinical and pathologic features of families with LRRK2-associated Parkinson’s disease. In: Riederer, P., Reichmann, H., Youdim, M.B.H., Gerlach, M. (eds) Parkinson’s Disease and Related Disorders. Journal of Neural Transmission. Supplementa, vol 70. Springer, Vienna . https://doi.org/10.1007/978-3-211-45295-0_34
Download citation
DOI: https://doi.org/10.1007/978-3-211-45295-0_34
Publisher Name: Springer, Vienna
Print ISBN: 978-3-211-28927-3
Online ISBN: 978-3-211-45295-0
eBook Packages: MedicineMedicine (R0)