Parkin mutations and phenotypic features in Czech patients with early-onset Parkinson's disease

被引：0

作者：

Fiala, Ondrej ^{[1
,2
,3
]}

Pospisilova, Lenka ^{[2
,4
]}

Prochazkova, Jana ^{[2
,4
]}

Matejckova, Milada ^{[5
]}

Martasek, Pavel ^{[2
,4
]}

Novakova, Lucie ^{[1
,2
]}

Roth, Jan ^{[1
,2
]}

Ruzicka, Evzen ^{[1
,2
]}

机构：

[1] Charles Univ Prague, Dept Neurol, Fac Med 1, Prague 12000 2, Czech Republic

[2] Gen Teaching Hosp, Prague 12000 2, Czech Republic

[3] Univ Marburg, Dept Expt Neurol, Marburg, Germany

[4] Charles Univ Prague, Dept Pediat, Fac Med 1, Prague 12000 2, Czech Republic

[5] Thomayers Univ Hosp, Dept Pathol & Mol Med, Prague, Czech Republic

来源：

NEUROENDOCRINOLOGY LETTERS | 2010年 / 31卷 / 02期

关键词：

early-onset Parkinson's disease; genotype; phenotype; mutations; polymorphisms; parkin; Czech; GENE; ASSOCIATION; SUSCEPTIBILITY; POLYMORPHISMS; DYSFUNCTION; DIAGNOSIS; COMMON;

D O I：

暂无

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

OBJECTIVES: Mutations in several genes such as parkin can be detected in up to 20% of patients with early-onset Parkinson's disease (EOPD). The aim of our study was to determine the frequency of parkin alterations and phenotypic characteristics in Czech EOPD patients. METHODS: A total of 45 EOPD individuals (age at onset <45 years) were phenotyped and screened for parkin mutations. RESULTS: In total, 19 patients (42.2%) were carriers of previously described heterozygous genetic alterations. Parkin mutations (Ex2del, R402C) were identified in two (4.4%) cases, non-pathogenic variant A82E plus polymorphism D394N occurred in one (2.2%) patient and parkin polymorphisms (3xS167N, 1xR334C, 7xV380L, 4xD394N) were found in 15 (34.9%) individuals. Furthermore, the G2019S mutation in the LRRK2 gene was found in one (2.2%) subject. CONCLUSION: The clinical characteristics of our patients correspond to previous descriptions of EOPD phenotype. This is the first report on EOPD-associated genetic alterations among Czech patients. Our results support the hypothesis that single heterozygous parkin variants may act as risk factors for EOPD.

引用

页码：187 / 192

页数：6

共 36 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] Structure of the Parkin in-between-ring domain provides insights for E3-ligase dysfunction in autosomal recessive Parkinson's disease [J].

Beasley, Steven A. ;

Hristova, Ventzislava A. ;

Shaw, Gary S. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (09) :3095-3100

[3] Novel parkin mutations detected in patients with early-onset Parkinson's disease [J].

Bertoli-Avella, AM ;

Giroud-Benitez, JL ;

Akyol, A ;

Barbosa, E ;

Schaap, O ;

van der Linde, HC ;

Martignoni, E ;

Lopiano, L ;

Lamberti, P ;

Fincati, E ;

Antonini, A ;

Stocchi, F ;

Montagna, P ;

Squitieri, F ;

Marini, P ;

Abbruzzese, G ;

Fabbrini, G ;

Marconi, M ;

Libera, AD ;

Trianni, G ;

Guidi, M ;

De Gaetano, A ;

Maegawa, GB ;

De Leo, A ;

Gallai, V ;

de Rosa, G ;

Vanacore, N ;

Meco, G ;

van Duijn, CM ;

Oostra, BA ;

Heutink, P ;

Bonifati, V .

MOVEMENT DISORDERS, 2005, 20 (04) :424-431

[4] Parkin polymorphisms:: risk for Parkinson's disease in Indian population [J].

Biswas, A. ;

Maulik, M. ;

Das, S. K. ;

Ray, K. ;

Ray, J. .

CLINICAL GENETICS, 2007, 72 (05) :484-486

[5] Early-onset Parkinson's disease caused by a novel parkin mutation in a genetic isolate from north-eastern Brazil [J].

Chien, HF ;

Rohé, CF ;

Costa, MDL ;

Breedveld, GJ ;

Oostra, BA ;

Barbosa, ER ;

Bonifati, V .

NEUROGENETICS, 2006, 7 (01) :13-19

[6] RING finger 1 mutations in Parkin produce altered localization of the protein [J].

Cookson, MR ;

Lockhart, PJ ;

O'Farrell, C ;

Schlossmacher, M ;

Farrer, MJ .

HUMAN MOLECULAR GENETICS, 2003, 12 (22) :2957-2965

[7] Epidemiology of Parkinson's disease [J].

de Lau, Lonneke M. L. ;

Breteler, Monique M. B. .

LANCET NEUROLOGY, 2006, 5 (06) :525-535

[8] Substantia nigra hyperechogenicity correlates with clinical status and number of Parkin mutated alleles [J].

Hagenah, Johann M. ;

Koenig, Inke R. ;

Becker, Bjoern ;

Hilker, Ruediger ;

Kasten, Meike ;

Hedrich, Katja ;

Pramstaller, Peter P. ;

Klein, Christine ;

Seidel, Guenter .

JOURNAL OF NEUROLOGY, 2007, 254 (10) :1407-1413

[9] 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

[10] The importance of gene dosage studies:: mutational analysis of the parkin gene in early-onset parkinsonism [J].

Hedrich, K ;

Kann, M ;

Lanthaler, AJ ;

Dalski, A ;

Eskelson, C ;

Landt, F ;

Schwinger, E ;

Vieregge, P ;

Lang, AE ;

Breakefield, XO ;

Ozelius, LJ ;

Pramstaller, PP ;

Klein, C .

HUMAN MOLECULAR GENETICS, 2001, 10 (16) :1649-1656

← 1 2 3 4 →