Prevalence and clinical features of common LRRK2 mutations in Australians with Parkinson's disease

被引:34
作者
Huang, Yue
Halliday, Glenda M.
Vandebona, Himesha
Mellick, George D.
Mastaglia, Frank
Stevens, Julia
Kwok, John
Garlepp, Michael
Silburn, Peter A.
Horne, Malcolm K.
Kotschet, Katya
Venn, Alison
Rowe, Dominic B.
Rubio, Justin P.
Sue, Carolyn M.
机构
[1] Royal N Shore Hosp, Kolling Inst Med Res, Dept Neurol & Neurogenet, St Leonards, NSW 2065, Australia
[2] Univ Sydney, St Leonards, NSW 2065, Australia
[3] Prince Wales Med Res Inst, Sydney, NSW, Australia
[4] Univ New S Wales, Kensington, NSW 2033, Australia
[5] Griffith Univ, Royal Brisbane & Womens Hosp, Dept Neurol, Eskitis Inst, Brisbane, Qld 4111, Australia
[6] Univ Western Australia, Nedlands, WA 6009, Australia
[7] Garvan Inst Med Res, Darlinghurst, NSW, Australia
[8] Curtin Univ Technol, Western Australian Biomed Res Inst, Bentley, WA 6102, Australia
[9] Univ Melbourne, Howard Florey Inst Expt Physiol & Med, Parkville, Vic 3052, Australia
[10] St Vincents Hosp, Melbourne, Vic, Australia
[11] Menzies Res Inst, Hobart, Tas, Australia
关键词
Parkinson's disease; LRRK2; G2019S; R1441G/C/H; A1442P;
D O I
10.1002/mds.21477
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
We determined the prevalence of two common leucine-rich repeat kinase 2 (LRRK2) gene mutations in Australian patients with Parkinson's disease (PD). Of 830 affected patients, eight were heterozygous for the G2019S mutation, and two were heterozygous for the R1441H (4,322 G > A) mutation. In addition, one familial patient had a novel A1442P (4,324 G > C) mutation. Haplotype analysis showed that all LRRK2 G2019S-positive individuals carried the common founder haplotype 1 and a putative founder haplotype for the R1441H mutation carriers. Clinically, patients with LRRK2 mutations had typical levodopa responsive Parkinsonism with tremor being the commonest presenting feature. Patients with the G2019S mutation in our series had a similar age of onset of symptoms when compared with patients with other LRRK2 mutations or sporadic PD, although they were more likely to have a family history of PD (2.4% of Australian patients with familial PD and 0.3% of Australian patients with sporadic PD). Our results demonstrate that the G2019S mutation carriers share the same ancestors who migrated to Australia originally from Europe and that other LRRK2 mutations (R1441H and A1442P) can be found in this population. (C) 2007 Movement Disorder Society.
引用
收藏
页码:982 / 989
页数:8
相关论文
共 36 条
[21]   Genetic screening for a single common LRRK2 mutation in familial Parkinson's disease [J].
Nichols, WC ;
Pankratz, N ;
Hernandez, D ;
Paisán-Ruíz, C ;
Jain, S ;
Halter, CA ;
Michaels, VE ;
Reed, T ;
Rudolph, A ;
Shults, CW ;
Singleton, A ;
Foroud, T .
LANCET, 2005, 365 (9457) :410-412
[22]   LRRK2 G2019S as a cause of Parkinson's disease in Ashkenazi Jews [J].
Ozelius, LJ ;
Senthil, G ;
Saunders-Pullman, R ;
Ohmann, E ;
Deligtisch, A ;
Tagliati, M ;
Hunt, AL ;
Klein, C ;
Henick, B ;
Hailpern, SM ;
Lipton, RB ;
Soto-Valencia, J ;
Risch, N ;
Bressman, SB .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 354 (04) :424-425
[23]   Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease [J].
Paisán-Ruíz, C ;
Jain, S ;
Evans, EW ;
Gilks, WP ;
Simón, J ;
van der Brug, M ;
de Munain, AL ;
Aparicio, S ;
Gil, AM ;
Khan, N ;
Johnson, J ;
Martinez, JR ;
Nicholl, D ;
Carrera, IM ;
Pena, AS ;
de Silva, R ;
Lees, A ;
Martí-Massó, JF ;
Pérez-Tur, J ;
Wood, NW ;
Singleton, AB .
NEURON, 2004, 44 (04) :595-600
[24]   Mutations in LRRK2 other than G2019S are rare in a north American-based sample of familial Parkinson's disease [J].
Pankratz, Nathan ;
Pauciulo, Michael W. ;
Elsaesser, Veronika E. ;
Marek, Diane K. ;
Halter, Cheryl A. ;
Rudolph, Alice ;
Shults, Clifford W. ;
Foroud, Tatiana ;
Nichols, William C. .
MOVEMENT DISORDERS, 2006, 21 (12) :2257-2260
[25]   Clinical heterogeneity of the LRRK2 G2019S mutation [J].
Papapetropoulos, Spiridon ;
Singer, Carlos ;
Ross, Owen A. ;
Toft, Mathias ;
Johnson, Joseph L. ;
Farrer, Matthew J. ;
Mash, Deborah C. .
ARCHIVES OF NEUROLOGY, 2006, 63 (09) :1242-1246
[26]   Structural details (kinks and non-α conformations) in transmembrane helices are intrahelically determined and can be predicted by sequence pattern descriptors [J].
Rigoutsos, I ;
Riek, P ;
Graham, RM ;
Novotny, J .
NUCLEIC ACIDS RESEARCH, 2003, 31 (15) :4625-4631
[27]   Lrrk2 R1441 substitution and progressive supranuclear palsy [J].
Ross, OA ;
Whittle, AJ ;
Cobb, SA ;
Hulihan, MM ;
Lincoln, SJ ;
Toft, M ;
Farrer, MJ ;
Dickson, DW .
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 2006, 32 (01) :23-25
[28]   The LRRK2 Gly2385Arg variant is associated with Parkinson's disease:: genetic and functional evidence [J].
Tan, E. K. ;
Zhao, Y. ;
Skipper, L. ;
Tan, M. G. ;
Di Fonzo, A. ;
Sun, L. ;
Fook-Chong, S. ;
Tang, S. ;
Chua, E. ;
Yuen, Y. ;
Tan, L. ;
Pavanni, R. ;
Wong, M. C. ;
Kolatkar, P. ;
Lu, C. S. ;
Bonifati, V. ;
Liu, J. J. .
HUMAN GENETICS, 2007, 120 (06) :857-863
[29]   The G2019S LRRK2 mutation is uncommon in an Asian cohort of Parkinson's disease patients [J].
Tan, EK ;
Shen, H ;
Tan, LCS ;
Farrer, A ;
Yew, K ;
Chua, E ;
Jamora, RD ;
Puvan, K ;
Puong, KY ;
Zhao, Y ;
Pavanni, R ;
Wong, MC ;
Yih, Y ;
Skipper, L ;
Liu, JJ .
NEUROSCIENCE LETTERS, 2005, 384 (03) :327-329
[30]   LRRK2: a common pathway for parkinsonism, pathogenesis and prevention? [J].
Taylor, JP ;
Mata, IF ;
Farrer, MJ .
TRENDS IN MOLECULAR MEDICINE, 2006, 12 (02) :76-82