Parkin disease in a Brazilian kindred: Manifesting heterozygotes and clinical follow-up over 10 years

被引:28
作者
Khan, NL
Horta, W
Eunson, L
Graham, E
Johnson, JO
Chang, S
Davis, M
Singleton, A
Wood, NW
Lees, AJ
机构
[1] Royal Free Hosp, Reta Lila Weston Unit Neurol Studies, London W1T 4JF, England
[2] Univ Coll Med Sch, London W1T 4JF, England
[3] Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England
[4] Univ Fed Ceara, Hosp Univ Walter Cantidio, Serv Neurol, Fortaleza, Ceara, Brazil
[5] Univ Fed Ceara, Dept Movement Disorders, Fortaleza, Ceara, Brazil
[6] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA
关键词
manifesting carriers; haploinsufficiency; isolated population;
D O I
10.1002/mds.20335
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
We report on a large Brazilian kindred with young-onset parkinsonism due to either a homozygous or heterozygous mutation in parkin. A total of 6 members were affected: 5 were homozygous and 1 heterozygous for a deletion in exon 4. Two other heterozygotes also had extrapyramidal signs. All affected subjects showed characteristic features of parkin disease with foot dystonia and an excellent response to levodopa complicated by motor fluctuations and dyskinesia within 3 years of therapy. Careful clinical follow-up over 10 years showed the phenotype was similar in all the homozygotes with asymmetrical limb bradykinesia and early walking difficulties. Some acceleration of disability was observed in some of the cases as they entered the third decade of illness, but dementia was absent. (c) 2004 Movement Disorder Society.
引用
收藏
页码:479 / 484
页数:6
相关论文
共 20 条
[1]   A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe [J].
Abbas, N ;
Lücking, CB ;
Ricard, S ;
Dürr, A ;
Bonifati, V ;
De Michele, G ;
Bouley, S ;
Vaughan, JR ;
Gasser, T ;
Marconi, R ;
Broussolle, E ;
Brefel-Courbon, C ;
Harhangi, BS ;
Oostra, AB ;
Fabrizio, E ;
Böhme, GA ;
Pradier, L ;
Wood, NW ;
Filla, A ;
Meco, G ;
Denefle, P ;
Agid, Y ;
Brice, A .
HUMAN MOLECULAR GENETICS, 1999, 8 (04) :567-574
[2]   LATE PROGRESSION OF POST-ENCEPHALITIC PARKINSONS SYNDROME [J].
CALNE, DB ;
LEES, AJ .
CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES, 1988, 15 (02) :135-138
[3]   Lewy bodies and parkinsonism in families with parkin mutations [J].
Farrer, M ;
Chan, P ;
Chen, R ;
Tan, L ;
Lincoln, S ;
Hernandez, D ;
Forno, L ;
Gwinn-Hardy, K ;
Petrucelli, L ;
Hussey, J ;
Singleton, A ;
Tanner, C ;
Hardy, J ;
Langston, JW .
ANNALS OF NEUROLOGY, 2001, 50 (03) :293-300
[4]   THE RELEVANCE OF THE LEWY BODY TO THE PATHOGENESIS OF IDIOPATHIC PARKINSONS-DISEASE [J].
GIBB, WRG ;
LEES, AJ .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 1988, 51 (06) :745-752
[5]  
Hilker R, 2001, ANN NEUROL, V49, P367, DOI 10.1002/ana.74
[6]   Olfaction differentiates parkin disease from early-onset parkinsonism and Parkinson disease [J].
Khan, NL ;
Katzenschlager, R ;
Watt, H ;
Bhatia, KP ;
Wood, NW ;
Quinn, N ;
Lees, AJ .
NEUROLOGY, 2004, 62 (07) :1224-1226
[7]   Parkin disease: a phenotypic study of a large case series [J].
Khan, NL ;
Graham, E ;
Critchley, P ;
Schrag, AE ;
Wood, NW ;
Lees, AJ ;
Bhatia, KP ;
Quinn, N .
BRAIN, 2003, 126 :1279-1292
[8]   Progression of nigrostriatal dysfunction in a parkin kindred:: an [18F] dopa PET and clinical study [J].
Khan, NL ;
Brooks, DJ ;
Pavese, N ;
Sweeney, MG ;
Wood, NW ;
Lees, AJ ;
Piccini, P .
BRAIN, 2002, 125 :2248-2256
[9]  
KHAN NL, IN PRESS NEUROLOGY
[10]   Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism [J].
Kitada, T ;
Asakawa, S ;
Hattori, N ;
Matsumine, H ;
Yamamura, Y ;
Minoshima, S ;
Yokochi, M ;
Mizuno, Y ;
Shimizu, N .
NATURE, 1998, 392 (6676) :605-608