Mutations in LRRK2 Cause Autosomal-Dominant Parkinsonism with Pleomorphic Pathology
Alexander Zimprich,Alexander Zimprich,Saskia Biskup,Petra Leitner,Peter Lichtner,Matthew J. Farrer,Sarah Lincoln,Jennifer M. Kachergus,Mary M. Hulihan,Ryan J. Uitti,Donald B. Calne,A. Jon Stoessl,Ronald F. Pfeiffer,Nadja Patenge,Iria Carballo Carbajal,Peter Vieregge,Friedrich Asmus,Bertram Müller-Myhsok,Dennis W. Dickson,Thomas Meitinger,Tim M. Strom,Zbigniew K. Wszolek,Thomas Gasser +22 more
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TLDR
High-resolution recombination mapping and candidate gene sequencing in 46 families found six disease-segregating mutations in a gene encoding a large, multifunctional protein, LRRK2 (leucine-rich repeat kinase 2), which may be central to the pathogenesis of several major neurodegenerative disorders associated with parkinsonism.About:
This article is published in Neuron.The article was published on 2004-11-18 and is currently open access. It has received 2757 citations till now. The article focuses on the topics: Parkinsonism & Lewy body.read more
Citations
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Pathological roles of MAPK signaling pathways in human diseases
Eunkyung Kim,Eui Ju Choi +1 more
TL;DR: Recent findings on the roles of MAPK signaling pathways in human disorders, focusing on cancer and neurodegenerative diseases including AD, PD, and ALS are summarized.
Journal ArticleDOI
Genome-wide association study reveals genetic risk underlying Parkinson's disease
Javier Simón-Sánchez,Claudia Schulte,Jose Bras,Jose Bras,Manu Sharma,J. Raphael Gibbs,J. Raphael Gibbs,Daniela Berg,Coro Paisán-Ruiz,Peter Lichtner,Sonja W. Scholz,Sonja W. Scholz,Dena G. Hernandez,Dena G. Hernandez,Rejko Krüger,Monica Federoff,Christine Klein,Alison Goate,Joel S. Perlmutter,Michael Bonin,Mike A. Nalls,Thomas Illig,Christian Gieger,Henry Houlden,Michael Steffens,Michael S. Okun,Brad A. Racette,Mark R. Cookson,Kelly D. Foote,Hubert H. Fernandez,Bryan J. Traynor,Stefan Schreiber,Sampath Arepalli,Ryan R. Zonozi,Katrina Gwinn,Marcel P. van der Brug,Marcel P. van der Brug,Grisel Lopez,Stephen J. Chanock,Arthur Schatzkin,Yikyung Park,Albert R. Hollenbeck,Jianjun Gao,Xuemei Huang,Nicholas W. Wood,Delia Lorenz,Günther Deuschl,Honglei Chen,Olaf Riess,John Hardy,Andrew B. Singleton,Thomas Gasser +51 more
TL;DR: It is demonstrated that an unequivocal role for common genetic variants in the etiology of typical PD and population-specific genetic heterogeneity in this disease is suggested, and supporting evidence that common variation around LRRK2 modulates risk for PD is provided.
Journal ArticleDOI
Initial genome sequencing and analysis of multiple myeloma
Michael A Chapman,Michael S. Lawrence,Jonathan J Keats,Kristian Cibulskis,Carrie Sougnez,Anna C. Schinzel,Christina L. Harview,Jean Philippe Brunet,Gregory J. Ahmann,Mazhar Adli,Mazhar Adli,Kenneth C. Anderson,Kristin G. Ardlie,Daniel Auclair,Angela Baker,P. Leif Bergsagel,Bradley E. Bernstein,Bradley E. Bernstein,Bradley E. Bernstein,Yotam Drier,Yotam Drier,Rafael Fonseca,Stacey Gabriel,Craig C. Hofmeister,Sundar Jagannath,Andrzej Jakubowiak,Amrita Krishnan,Joan Levy,Ted Liefeld,Sagar Lonial,Scott Mahan,Bunmi Mfuko,Stefano Monti,Louise M. Perkins,Robb Onofrio,Trevor J. Pugh,S. Vincent Rajkumar,Alex H. Ramos,David S. Siegel,Andrey Sivachenko,A. Keith Stewart,Suzanne Trudel,Ravi Vij,Douglas Voet,Wendy Winckler,Todd Zimmerman,John D. Carpten,Jeff Trent,William C. Hahn,William C. Hahn,Levi A. Garraway,Levi A. Garraway,Matthew Meyerson,Matthew Meyerson,Eric S. Lander,Eric S. Lander,Eric S. Lander,Gad Getz,Todd R. Golub +58 more
TL;DR: The massively parallel sequencing of 38 tumour genomes and their comparison to matched normal DNAs indicates that cancer genome sequencing of large collections of samples will yield new insights into cancer not anticipated by existing knowledge.
Journal ArticleDOI
Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study
Daniel G. Healy,Mario Falchi,Sean S. O'Sullivan,Vincenzo Bonifati,Alexandra Durr,Susan B. Bressman,Alexis Brice,Jan O. Aasly,Cyrus P. Zabetian,Stefano Goldwurm,Joaquim J. Ferreira,Eduardo Tolosa,Denise M. Kay,Christine Klein,David R. Williams,Connie Marras,Anthony E. Lang,Zbigniew K. Wszolek,José Berciano,Anthony H.V. Schapira,Timothy Lynch,Kailash P. Bhatia,Thomas Gasser,Andrew J. Lees,Andrew J. Lees,Nicholas W. Wood +25 more
TL;DR: Mutations in LRRK2 are a clinically relevant cause of PD that merit testing in patients with hereditary PD and in subgroups of patients with PD, but this knowledge should be applied with caution in the diagnosis and counselling of patients.
Journal ArticleDOI
Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease
Wataru Satake,Yuko Nakabayashi,Yuko Nakabayashi,Ikuko Mizuta,Ikuko Mizuta,Yushi Hirota,Yushi Hirota,Chiyomi Ito,Chiyomi Ito,Michiaki Kubo,Takahisa Kawaguchi,Tatsuhiko Tsunoda,Masahiko Watanabe,Atsushi Takeda,Hiroyuki Tomiyama,Kenji Nakashima,Kazuko Hasegawa,Fumiya Obata,Takeo Yoshikawa,Hideshi Kawakami,Saburo Sakoda,Mitsutoshi Yamamoto,Nobutaka Hattori,Miho Murata,Yusuke Nakamura,Tatsushi Toda,Tatsushi Toda +26 more
TL;DR: The results identify two new PD susceptibility loci, show involvement of autosomal dominant parkinsonism loci in typical PD and suggest that population differences contribute to genetic heterogeneity in PD.
References
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Mutation in the α-synuclein gene identified in families with Parkinson's disease
Mihael H. Polymeropoulos,Christian Lavedan,Elisabeth Leroy,Susan E. Ide,Anindya Dehejia,Amalia Dutra,Brian L. Pike,Holly Root,Jeffrey Rubenstein,Rebecca Boyer,Edward S. Stenroos,Settara C. Chandrasekharappa,Aglaia Athanassiadou,Theodore Papapetropoulos,William G. Johnson,Alice Lazzarini,Roger C. Duvoisin,Giuseppe Di Iorio,Lawrence I. Golbe,Robert L. Nussbaum +19 more
TL;DR: A mutation was identified in the α-synuclein gene, which codes for a presynaptic protein thought to be involved in neuronal plasticity, in the Italian kindred and in three unrelated families of Greek origin with autosomal dominant inheritance for the PD phenotype.
Journal ArticleDOI
Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism
Tohru Kitada,Shuichi Asakawa,Nobutaka Hattori,Hiroto Matsumine,Yasuhiro Yamamura,Shinsei Minoshima,Masayuki Yokochi,Yoshikuni Mizuno,Nobuyoshi Shimizu +8 more
TL;DR: Mutations in the newly identified gene appear to be responsible for the pathogenesis of Autosomal recessive juvenile parkinsonism, and the protein product is named ‘Parkin’.
Journal ArticleDOI
α-Synuclein Locus Triplication Causes Parkinson's Disease
Andrew B. Singleton,Matthew J. Farrer,Joshua C. Johnson,Amanda Singleton,Stephen Hague,Jennifer M. Kachergus,Mary M. Hulihan,Terhi Peuralinna,Amalia Dutra,Robert L. Nussbaum,Sarah Lincoln,Anthony Crawley,Melissa Hanson,Demetrius M. Maraganore,Charles H. Adler,Mark R. Cookson,Manfred D. Muenter,Melisa J. Baptista,David Miller,J. Blancato,John Hardy,Katrina Gwinn-Hardy +21 more
TL;DR: In this article, the α-synuclein was identified as the major component of Lewy bodies, the pathological hallmark of Parkinson's disease, and of glial cell cytoplasmic inclusions.
Journal ArticleDOI
Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17
Mike Hutton,Corinne Lendon,Patrizia Rizzu,Matt Baker,Susanne Froelich,Susanne Froelich,Henry Houlden,Stuart Pickering-Brown,Sumitra Chakraverty,Adrian M. Isaacs,Andrew Grover,J. Hackett,Jennifer Adamson,Sarah Lincoln,Dennis W. Dickson,Peter Davies,Ronald C. Petersen,M. Stevens,E. De Graaff,E. Wauters,J. Van Baren,M. Hillebrand,Marijke Joosse,J. M. Kwon,Petra Nowotny,Lien Kuei Che,Joanne Norton,John C. Morris,L. A. Reed,John Q. Trojanowski,Hans Basun,Lars Lannfelt,M. Neystat,Stanley Fahn,Frances Dark,Tony Tannenberg,Peter R. Dodd,Nicholas K. Hayward,John B.J. Kwok,Peter R. Schofield,Athena Andreadis,Julie S. Snowden,David Craufurd,David Neary,F. Owen,Ben A. Oostra,John Hardy,Alison Goate,J. C. van Swieten,David M. A. Mann,Timothy Lynch,Peter Heutink +51 more
TL;DR: In this paper, the authors sequenced tau in FTDP-17 families and identified three missense mutations (G272V, P301L and R406W) and three mutations in the 5' splice site of exon in
Journal ArticleDOI
Hereditary Early-Onset Parkinson's Disease Caused by Mutations in PINK1
Eriza Maria Valente,Patrick M. Abou-Sleiman,Viviana Caputo,Miratul M. K. Muqit,Kirsten Harvey,Suzana Gispert,Zeeshan Ali,Domenico Del Turco,Anna Rita Bentivoglio,Daniel G. Healy,Alberto Albanese,Robert L. Nussbaum,Rafael González-Maldonado,Thomas Deller,S Salvi,Pietro Cortelli,William P. Gilks,David S. Latchman,Roberk J. Harvey,Bruno Dallapiccola,Georg Auburger,Nicholas W. Wood +21 more
TL;DR: The identification of two homozygous mutations affecting the PINK1 kinase domain in three consanguineous PARK6 families provide a direct molecular link between mitochondria and the pathogenesis of PD.
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Mutation in the α-synuclein gene identified in families with Parkinson's disease
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