Comprehensive screening of a North American Parkinson's disease cohort for LRRK2 mutation

Janel Johnson; Coro Paisán-Ruíz; Grisel Lopez; Cynthia Crews; Angela Britton; Roniel Malkani; E. Whitney Evans; Aideen McInerney-Leo; Shushant Jain; Robert L. Nussbaum; Kelly D. Foote; Ronald J. Mandel; Anthony Crawley; Sharon Reimsnider; Hubert H. Fernandez; Michael S. Okun; Katrina Gwinn-Hardy; Andrew B. Singleton

doi:10.1159/000105160

Comprehensive screening of a North American Parkinson's disease cohort for LRRK2 mutation

Janel Johnson, Coro Paisán-Ruíz, Grisel Lopez, Cynthia Crews, Angela Britton, Roniel Malkani, E. Whitney Evans, Aideen McInerney-Leo, Shushant Jain, Robert L. Nussbaum, Kelly D. Foote, Ronald J. Mandel, Anthony Crawley, Sharon Reimsnider, Hubert H. Fernandez, Michael S. Okun, Katrina Gwinn-Hardy, Andrew B. Singleton^*

^*Corresponding author for this work

Neurology

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

Abstract

Background: Recently, mutations in LRRK2 encoding the protein dardarin have been linked to an autosomal dominant form of parkinsonism. Objective: To identify mutations causing Parkinson's disease (PD) in a cohort of North Americans with familial PD. Methods: We sequenced exons 1-51 of LRRK2 in 79 unrelated North American PD patients reporting a family history of the disease. Results: One patient had a missense mutation (Thr2356Ile) while two others had the common Gly2019Ser mutation. In addition, 1 patient had a 4-bp deletion in close proximity to the exon 19 splice donor (IVS20+4delGTAA) that in vitro abrogates normal splicing. Conclusions: Our observations in the 79 North American patients indicate that mutations in LRRK2 are associated with approximately 5% of PD cases with a positive family history. The results also show that G2019S represents approximately half of the LRRK2 mutations in United States PD cases with a family history of the disease. We have identified two novel mutations in LRRK2.

Original language	English (US)
Pages (from-to)	386-391
Number of pages	6
Journal	Neurodegenerative Diseases
Volume	4
Issue number	5
DOIs	https://doi.org/10.1159/000105160
State	Published - Jul 2007

Funding

Keywords

Dardarin encoding
LRRK2, Parkinson's disease
Mutation

ASJC Scopus subject areas

Clinical Neurology
Neurology

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10.1159/000105160

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Johnson, J., Paisán-Ruíz, C., Lopez, G., Crews, C., Britton, A., Malkani, R., Evans, E. W., McInerney-Leo, A., Jain, S., Nussbaum, R. L., Foote, K. D., Mandel, R. J., Crawley, A., Reimsnider, S., Fernandez, H. H., Okun, M. S., Gwinn-Hardy, K., & Singleton, A. B. (2007). Comprehensive screening of a North American Parkinson's disease cohort for LRRK2 mutation. Neurodegenerative Diseases, 4(5), 386-391. https://doi.org/10.1159/000105160

@article{6fb409f7a9c4474ab0dde1e0f747dbb5,

title = "Comprehensive screening of a North American Parkinson's disease cohort for LRRK2 mutation",

abstract = "Background: Recently, mutations in LRRK2 encoding the protein dardarin have been linked to an autosomal dominant form of parkinsonism. Objective: To identify mutations causing Parkinson's disease (PD) in a cohort of North Americans with familial PD. Methods: We sequenced exons 1-51 of LRRK2 in 79 unrelated North American PD patients reporting a family history of the disease. Results: One patient had a missense mutation (Thr2356Ile) while two others had the common Gly2019Ser mutation. In addition, 1 patient had a 4-bp deletion in close proximity to the exon 19 splice donor (IVS20+4delGTAA) that in vitro abrogates normal splicing. Conclusions: Our observations in the 79 North American patients indicate that mutations in LRRK2 are associated with approximately 5% of PD cases with a positive family history. The results also show that G2019S represents approximately half of the LRRK2 mutations in United States PD cases with a family history of the disease. We have identified two novel mutations in LRRK2.",

keywords = "Dardarin encoding, LRRK2, Parkinson's disease, Mutation",

author = "Janel Johnson and Coro Pais{\'a}n-Ru{\'i}z and Grisel Lopez and Cynthia Crews and Angela Britton and Roniel Malkani and Evans, {E. Whitney} and Aideen McInerney-Leo and Shushant Jain and Nussbaum, {Robert L.} and Foote, {Kelly D.} and Mandel, {Ronald J.} and Anthony Crawley and Sharon Reimsnider and Fernandez, {Hubert H.} and Okun, {Michael S.} and Katrina Gwinn-Hardy and Singleton, {Andrew B.}",

year = "2007",

month = jul,

doi = "10.1159/000105160",

language = "English (US)",

volume = "4",

pages = "386--391",

journal = "Neurodegenerative Diseases",

issn = "1660-2854",

publisher = "S. Karger AG",

number = "5",

}

Johnson, J, Paisán-Ruíz, C, Lopez, G, Crews, C, Britton, A, Malkani, R, Evans, EW, McInerney-Leo, A, Jain, S, Nussbaum, RL, Foote, KD, Mandel, RJ, Crawley, A, Reimsnider, S, Fernandez, HH, Okun, MS, Gwinn-Hardy, K & Singleton, AB 2007, 'Comprehensive screening of a North American Parkinson's disease cohort for LRRK2 mutation', Neurodegenerative Diseases, vol. 4, no. 5, pp. 386-391. https://doi.org/10.1159/000105160

TY - JOUR

T1 - Comprehensive screening of a North American Parkinson's disease cohort for LRRK2 mutation

AU - Johnson, Janel

AU - Paisán-Ruíz, Coro

AU - Lopez, Grisel

AU - Crews, Cynthia

AU - Britton, Angela

AU - Malkani, Roniel

AU - Evans, E. Whitney

AU - McInerney-Leo, Aideen

AU - Jain, Shushant

AU - Nussbaum, Robert L.

AU - Foote, Kelly D.

AU - Mandel, Ronald J.

AU - Crawley, Anthony

AU - Reimsnider, Sharon

AU - Fernandez, Hubert H.

AU - Okun, Michael S.

AU - Gwinn-Hardy, Katrina

AU - Singleton, Andrew B.

PY - 2007/7

Y1 - 2007/7

N2 - Background: Recently, mutations in LRRK2 encoding the protein dardarin have been linked to an autosomal dominant form of parkinsonism. Objective: To identify mutations causing Parkinson's disease (PD) in a cohort of North Americans with familial PD. Methods: We sequenced exons 1-51 of LRRK2 in 79 unrelated North American PD patients reporting a family history of the disease. Results: One patient had a missense mutation (Thr2356Ile) while two others had the common Gly2019Ser mutation. In addition, 1 patient had a 4-bp deletion in close proximity to the exon 19 splice donor (IVS20+4delGTAA) that in vitro abrogates normal splicing. Conclusions: Our observations in the 79 North American patients indicate that mutations in LRRK2 are associated with approximately 5% of PD cases with a positive family history. The results also show that G2019S represents approximately half of the LRRK2 mutations in United States PD cases with a family history of the disease. We have identified two novel mutations in LRRK2.

AB - Background: Recently, mutations in LRRK2 encoding the protein dardarin have been linked to an autosomal dominant form of parkinsonism. Objective: To identify mutations causing Parkinson's disease (PD) in a cohort of North Americans with familial PD. Methods: We sequenced exons 1-51 of LRRK2 in 79 unrelated North American PD patients reporting a family history of the disease. Results: One patient had a missense mutation (Thr2356Ile) while two others had the common Gly2019Ser mutation. In addition, 1 patient had a 4-bp deletion in close proximity to the exon 19 splice donor (IVS20+4delGTAA) that in vitro abrogates normal splicing. Conclusions: Our observations in the 79 North American patients indicate that mutations in LRRK2 are associated with approximately 5% of PD cases with a positive family history. The results also show that G2019S represents approximately half of the LRRK2 mutations in United States PD cases with a family history of the disease. We have identified two novel mutations in LRRK2.

KW - Dardarin encoding

KW - LRRK2, Parkinson's disease

KW - Mutation

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U2 - 10.1159/000105160

DO - 10.1159/000105160

M3 - Article

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AN - SCOPUS:34547231540

SN - 1660-2854

VL - 4

SP - 386

EP - 391

JO - Neurodegenerative Diseases

JF - Neurodegenerative Diseases

IS - 5

ER -

Comprehensive screening of a North American Parkinson's disease cohort for LRRK2 mutation

Abstract

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Keywords

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