Parkinson's disease and LRRK2:: Frequency of a common mutation in US movement disorder clinics

被引:73
作者
Kay, DM
Zabetian, CP
Factor, SA
Nutt, JG
Samii, A
Griffith, A
Bird, TD
Kramer, P
Higgins, DS
Payami, H
机构
[1] New York State Dept Hlth, Wadsworth Ctr, Genom Inst, Albany, NY 12201 USA
[2] VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA
[3] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA
[4] Albany Med Ctr, Parkinsons Dis & Movement Disorder Clin, Albany, NY USA
[5] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA
[6] Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA
[7] VA Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA
[8] Evergreen Hosp, Med Ctr, Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA
关键词
Parkinson's disease; LRRK2 G2019S mutation; genotype-phenotype correlation; family history; age at onset; geography;
D O I
10.1002/mds.20751
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
The G2019S mutation in the LRRK2 gene is reportedly a common cause of familial Parkinson's disease (PD) and may also have a significant role in nonfamilial PD. The objective of this study was to assess mutation carrier frequency in PD patients from movement disorder clinics in the United States, stratified by family history, age at onset, and geography, to determine carrier frequency in a large and well-characterized control Population; to examine segregation Of mutation in families of patients; and to correlate genotype with clinical phenotype. One thousand four hundred twenty-five unrelated PD patients from movement disorder clinics in Oregon, Washington, and New York and 1,647 unrelated controls were Studied. The G2019S mutation was detected using a TaqMan assay and verified by sequencing. Eighteen of 1.425 patients and one of 1.647 controls had the mutation. Carrier frequency (+/- 2SE) in patients was 0.013 +/- 0.006 overall, 0.030 +/- 0.019 in familial PD, 0.007 +/- 0.005 in nonfamilial PD, 0.016 +/- 0.013 in early-onset PD. and 0.012 +/- 0.007 in late-onset PD. Geographic differences were insignificant. Age at onset of mutation carriers, ranged from 28 to 71 years. Mutation carriers were clinically indistinguishable from idiopathic PD. LRRK2 G2019S is the single most common pathogenic mutation linked to neurodegenerative disease to date. (C) 2006 Movement Disorder Society.
引用
收藏
页码:519 / 523
页数:5
相关论文
共 18 条
[1]   Clinical features of LRRK2-associated Parkinson's disease in Central Norway [J].
Aasly, JO ;
Toft, M ;
Fernandez-Mata, I ;
Kachergus, J ;
Hulihan, M ;
White, LR ;
Farrer, M .
ANNALS OF NEUROLOGY, 2005, 57 (05) :762-765
[2]   The current status of Alzheimer's disease genetics: what do we tell the patients? [J].
Bertram, L ;
Tanzi, RE .
PHARMACOLOGICAL RESEARCH, 2004, 50 (04) :385-396
[3]   Genetic and clinical identification of Parkinson's disease patients with LRRK2 G2019S mutation [J].
Deng, H ;
Le, WD ;
Guo, Y ;
Hunter, CB ;
Xie, WJ ;
Jankovic, J .
ANNALS OF NEUROLOGY, 2005, 57 (06) :933-934
[4]  
Di Fonzo A, 2005, LANCET, V365, P412
[5]   Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease - A meta-analysis [J].
Farrer, LA ;
Cupples, LA ;
Haines, JL ;
Hyman, B ;
Kukull, WA ;
Mayeux, R ;
Myers, RH ;
PericakVance, MA ;
Risch, N ;
vanDuijn, CM .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1997, 278 (16) :1349-1356
[6]   A new locus for Parkinson's disease (PARK8) maps to chromosome 12p11.2-q13.1 [J].
Funayama, M ;
Hasegawa, K ;
Kowa, H ;
Saito, M ;
Tsuji, S ;
Obata, F .
ANNALS OF NEUROLOGY, 2002, 51 (03) :296-301
[7]   Common LRRK2 mutation in idiopathic Parkinson's disease [J].
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 .
LANCET, 2005, 365 (9457) :415-416
[8]   Distribution, type, and origin of Parkin mutations:: Review and case studies [J].
Hedrich, K ;
Eskelson, C ;
Wilmot, B ;
Marder, K ;
Harris, J ;
Garrels, J ;
Meija-Santana, H ;
Vieregge, P ;
Jacobs, H ;
Bressman, SB ;
Lang, AE ;
Kann, M ;
Abbruzzese, G ;
Martinelli, P ;
Schwinger, E ;
Ozelius, LJ ;
Pramstaller, PP ;
Klein, C ;
Kramer, P .
MOVEMENT DISORDERS, 2004, 19 (10) :1146-1157
[9]   ACCURACY OF CLINICAL-DIAGNOSIS OF IDIOPATHIC PARKINSONS-DISEASE - A CLINICOPATHOLOGICAL STUDY OF 100 CASES [J].
HUGHES, AJ ;
DANIEL, SE ;
KILFORD, L ;
LEES, AJ .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 1992, 55 (03) :181-184
[10]   Identification of a novel LRRK2 mutation linked to autosomal dominant parkinsonism:: Evidence of a common founder across European populations [J].
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 .
AMERICAN JOURNAL OF HUMAN GENETICS, 2005, 76 (04) :672-680