Genetic screening for a single common LRRK2 mutation in familial Parkinson's disease
Abstract
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause some forms of autosomal dominant Parkinson's disease. We measured the frequency of a novel mutation (Gly2019 ser) in familial Parkinson's disease by screening genomic DNA of patients and controls. Of 767 affected individuals from 358 multiplex families, 35 (5%) individuals were either heterozygous (34) or homozygous (one) for the mutation, and had typical clinical findings of idiopathic Parkinson's disease. Thus, our results suggest that a single LRRK2 mutation causes Parkinson's disease in 5% of individuals with familial disease. Screening for this mutation should be a component of genetic testing for Parkinson's disease.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Mono-allelic GRN mutation carriers have lipofuscinosis accumulation similar to the NCLs.
“It was additionally observed that mono-allelic GRN mutation carriers have lipofuscinosis accumulation similar to the NCLs, suggesting overlapping disease processes.117”
From The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases (2025) · cites this paper as [117]
Cited by
Sorted by citations
Cognitive decline in Parkinson disease
Aarsland, D., Creese, B., Politis, M., Chaudhuri, K. R., ffytche, D. H., Weintraub, D., & Ballard, C. (2017) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.27 · Cited by 1,027 · see citing works
The diagnosis of Parkinson’s disease
Tolosa, E., Wenning, G., & Poewe, W. (2006) · The Lancet Neurology · doi:10.1016/s1474-4422(05)70285-4 · Cited by 902 · see citing works
Mitochondria in the aetiology and pathogenesis of Parkinson's disease
Schapira, A. H. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(07)70327-7 · Cited by 883 · see citing works
Parkinson’s disease: genetics and pathogenesis
Shulman, J. M., De Jager, P. L., & Feany, M. B. (2011) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-011110-130242 · Cited by 801 · see citing works
Ramonet, D., Daher, J. P. L., Lin, B. M., Stafa, K., Kim, J., Banerjee, R., Westerlund, M., Pletnikova, O., Glauser, L., Yang, L., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018568 · Cited by 405 · see citing works
di Domenico, A., Carola, G., Calatayud, C., Pons-Espinal, M., Muñoz, J. P., Richaud-Patin, Y., Fernandez-Carasa, I., Gut, M., Faella, A., Parameswaran, J., et al. (2019) · Stem Cell Reports · doi:10.1016/j.stemcr.2018.12.011 · Cited by 372 · see citing works
PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)
He, M., Cao, C., Ni, Z., Liu, Y., Song, P., Hao, S., He, Y., Sun, X., & Rao, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00999-9 · Cited by 283 · see citing works
Molecular pathogenesis of Parkinson's disease
Gandhi, S., & Wood, N. W. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi308 · Cited by 251 · see citing works
Henry, A. G., Aghamohammadzadeh, S., Samaroo, H., Chen, Y., Mou, K., Needle, E., & Hirst, W. D. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv314 · Cited by 235 · see citing works
Mitochondrial Medicine for Aging and Neurodegenerative Diseases
Reddy, P. H. (2008) · NeuroMolecular Medicine · doi:10.1007/s12017-008-8044-z · Cited by 230 · see citing works
Neuroinflammation in Parkinson's disease: role in neurodegeneration and tissue repair
Vivekanantham, S., Shah, S., Dewji, R., Dewji, A., Khatri, C., & Ologunde, R. (2015) · International Journal of Neuroscience · doi:10.3109/00207454.2014.982795 · Cited by 171 · see citing works
Paulsen, J. S., Nance, M., Kim, J.-I., Carlozzi, N. E., Panegyres, P. K., Erwin, C., Goh, A., McCusker, E., & Williams, J. K. (2013) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.08.003 · Cited by 168 · see citing works
Bonello, F., Hassoun, S.-M., Mouton-Liger, F., Shin, Y. S., Muscat, A., Tesson, C., Lesage, S., Beart, P. M., Brice, A., Krupp, J., et al. (2019) · Human Molecular Genetics · doi:10.1093/hmg/ddz004 · Cited by 163 · see citing works
Lane-Donovan, C., Paredes, M., & Kao, A. W. (2025) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2025.102854 · Cited by 3 · see citing works
- Authors
- Nichols, W. C., Pankratz, N., Hernandez, D., Paisán-Ruíz, C., Jain, S., Halter, C. A., Michaels, V. E., Reed, T., Rudolph, A., Shults, C. W., Singleton, A., & Foroud, T.
- Affiliations
- Cincinnati Children's Hospital Medical Center (US)
- Indiana University (US)
- National Institutes of Health (US)
- University of Rochester Medicine (US)
- University of California San Diego (US)
- Corresponding author
- Nichols, William C
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2005-01
- Volume
- 365
- Issue
- 9457
- Pages
- 410-412
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W2088528774
- Cited by
- 457
- References
- 0
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 10 · 2023: 12 · 2022: 12 · 2021: 13 · 2020: 11 · 2019: 24 · 2018: 16 · 2017: 11 · 2016: 6 · 2015: 15 · 2014: 18 · 2013: 14 · 2012: 14
- FWCI
- 40.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Ministerio de Educación Superior, Ciencia y Tecnología, República Dominicana (GEN2001-4851-C06-01)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- LRRK2, Parkinson's disease, familial Parkinson's disease, genetic screening, autosomal dominant inheritance, multiplex families, mutation frequency, genetic testing
- MeSH terms
- Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Adolescent, Adult, Aged, Aged, 80 and over, Genetic Testing, Genotype, Heterozygote, Homozygote, Humans, Male, Middle Aged, Parkinson Disease, Protein Serine-Threonine Kinases, Point Mutation, Genetic Predisposition to Disease
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
