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Motor Phenotype of LRRK2 G2019S Carriers in Early-Onset Parkinson Disease
被引:0
|作者:
Alcalay, Roy N.
[1
]
Mejia-Santana, Helen
[1
]
Tang, Ming Xin
[1
,3
]
Rosado, Llency
[1
]
Verbitsky, Miguel
[3
]
Kisselev, Sergey
[3
]
Ross, Barbara M.
[3
]
Louis, Elan D.
[1
,3
,4
,6
]
Comella, Cynthia L.
[12
]
Colcher, Amy
[16
]
Jennings, Danna
[14
]
Nance, Martha A.
[17
]
Bressman, Susan
[8
,9
]
Scott, William K.
[18
]
Tanner, Caroline
[21
]
Mickel, Susan F.
[20
]
Andrews, Howard F.
[10
]
Waters, Cheryl H.
[1
]
Fahn, Stanley
[1
]
Cote, Lucien J.
[4
]
Frucht, Steven J.
[1
]
Ford, Blair
[1
]
Rezak, Michael
[11
,13
]
Novak, Kevin
[11
,13
]
Friedman, Joseph H.
[22
,23
]
Pfeiffer, Ronald
[24
]
Marsh, Laura
[25
,26
]
Hiner, Bradley
[19
]
Siderowf, Andrew
[15
]
Caccappolo, Elise
[3
]
Ottman, Ruth
[4
,6
]
Clark, Lorraine N.
[2
,3
,5
]
Marder, Karen S.
[1
,3
,4
,7
]
机构:
[1] Columbia Univ, Dept Neurol, New York, NY 10032 USA
[2] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA
[3] Columbia Univ, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA
[4] Columbia Univ, Gertrude H Sergievsky Ctr, New York, NY 10032 USA
[5] Columbia Univ, Coll Phys & Surg, Ctr Human Genet, New York, NY 10032 USA
[6] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA
[7] Columbia Univ, Med Ctr, Dept Psychiat, New York, NY 10032 USA
[8] Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10467 USA
[9] Albert Einstein Coll Med, Beth Israel Med Ctr, Alan & Barbara Mirken Dept Neurol, Bronx, NY 10467 USA
[10] Albert Einstein Coll Med, Data Coordinating Ctr, New York State Psychiat Inst, Bronx, NY 10467 USA
[11] Northwestern Univ, Feinberg Sch Med, Dept Neurol, Chicago, IL USA
[12] Rush Univ, Dept Neurol, Movement Disorder Sect, Chicago, IL 60612 USA
[13] NorthShore Univ HealthSyst, Dept Neurol, Evanston, IL USA
[14] Inst Neurodegenerat Disorders, New Haven, CT USA
[15] Univ Penn Hlth Syst, Dept Neurol, Philadelphia, PA USA
[16] Univ Penn Hlth Syst, Parkinsons Dis & Movement Disorders Ctr, Penn Hosp, Philadelphia, PA USA
[17] Park Nicollet Clin, Struthers Parkinsons Ctr, Golden Valley, MN USA
[18] Univ Miami, Miller Sch Med, Dept Human Genet, Miami Inst Human Genom,Dr John T Macdonald Fdn, Miami, FL 33136 USA
[19] Med Coll Wisconsin, Milwaukee, WI 53226 USA
[20] Marshfield Clin Fdn Med Res & Educ, Dept Neurol, Marshfield, WI USA
[21] Parkinsons Inst, Sunnyvale, CA USA
[22] Parkinsons Dis & Movement Disorders Ctr NeuroHlth, Warwick, England
[23] Brown Univ, Warren Alpert Sch Med, Dept Clin Neurosci, Providence, RI 02912 USA
[24] Univ Tennessee, Ctr Hlth Sci, Coll Med, Dept Neurol, Memphis, TN 38163 USA
[25] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci & Neurol & Neurol Sci, Baltimore, MD USA
[26] Johns Hopkins Univ, Morris K Udall Parkinsons Dis Res Ctr Excellence, Baltimore, MD USA
基金:
美国国家卫生研究院;
关键词:
TREMOR-DOMINANT PARKINSONISM;
LEWY BODIES;
MUTATION;
DEMENTIA;
GENE;
SUBTYPE;
D O I:
暂无
中图分类号:
R74 [神经病学与精神病学];
学科分类号:
摘要:
Objective: To determine the motor phenotype of LRRK2 G2019S mutation carriers. LRRK2 mutation carriers were previously reported to manifest the tremor dominant motor phenotype, which has been associated with slower motor progression and less cognitive impairment compared with the postural instability and gait difficulty (PIGD) phenotype. Design: Cross-sectional observational study. Setting: Thirteen movement disorders centers. Participants: Nine hundred twenty-five early-onset Parkinson disease cases defined as age at onset younger than 51 years. Main Outcome Measures: LRRK2 mutation status and Parkinson disease motor phenotype: tremor dominant or PIGD. Demographic information, family history of Parkinson disease, and the Unified Parkinson's Disease Rating Scale score were collected on all participants. DNA samples were genotyped for LRRK2 mutations (G2019S, I2020T, R1441C, and Y1699C). Logistic regression was used to examine associations of G2019S mutation status with motor phenotype adjusting for disease duration, Ashkenazi Jewish ancestry, levodopa dose, and family history of Parkinson disease. Results: Thirty-four cases (3.7%) (14 previously reported) were G2019S carriers. No other mutations were found. Carriers were more likely to be Ashkenazi Jewish (55.9% vs 11.9%; P < .001) but did not significantly differ in any other demographic or disease characteristics. Carriers had a lower tremor score (P=.03) and were more likely to have a PIGD phenotype (92.3% vs 58.9%; P=.003). The association of the G2019S mutation with PIGD phenotype remained after controlling for disease duration and Ashkenazi Jewish ancestry (odds ratio, 17.7; P<.001). Conclusion: Early-onset Parkinson disease G2019S LRRK2 carriers are more likely to manifest the PIGD phenotype, which may have implications for disease course.
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页码:1517 / 1522
页数:6
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