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
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TLDR
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.Abstract:
Parkinson's disease (PD) is a common neurodegenerative disorder with a lifetime incidence of approximately 2 percent. A pattern of familial aggregation has been documented for the disorder, and it was recently reported that a PD susceptibility gene in a large Italian kindred is located on the long arm of human chromosome 4. 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. This finding of a specific molecular alteration associated with PD will facilitate the detailed understanding of the pathophysiology of the disorder.read more
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The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia.
Juan J. Zarranz,Javier Alegre,Juan Carlos Gómez-Esteban,Elena Lezcano,Raquel Ros,Israel Ampuero,Lídice Vidal,Janet Hoenicka,Olga Rodriguez,Begoña Atarés,Verónica Llorens,Estrella Gomez Tortosa,Teodoro del Ser,David G. Munoz,Justo García de Yébenes +14 more
TL;DR: Dementia with Lewy bodies is related to mutation of α‐synuclein, and the novel mutation, that substitutes a dicarboxylic amino acid, glutamic acid, with a basic amino acid in a much conserved area of the protein, is likely to produce severe disturbance of protein function.
Journal ArticleDOI
Clinical diagnostic criteria for dementia associated with Parkinson's disease.
Murat Emre,Dag Aarsland,Dag Aarsland,Richard G. Brown,David J. Burn,Charles Duyckaerts,Yoshikino Mizuno,Gerald A. Broe,Jeffrey L. Cummings,Dennis W. Dickson,Serge Gauthier,Jennifer G. Goldman,Christopher G. Goetz,Arnos Korczyn,Andrew J. Lees,Richard Levy,Irene Litvan,Ian G. McKeith,Warren Olanow,Werner Poewe,Niall Quinn,Christina Sampaio,Eduardo Tolosa,Bruno Dubois +23 more
TL;DR: Clinical diagnostic criteria for probable and possible PD‐D are proposed, characterized by impairment in attention, memory, executive and visuo‐spatial functions, behavioral symptoms such as affective changes, hallucinations, and apathy are frequent.
Journal ArticleDOI
Interleukin-1 polymorphisms associated with increased risk of gastric cancer
Emad M. El-Omar,Emad M. El-Omar,Mary Carrington,Wong Ho Chow,Kenneth E.L. McColl,Jay H. Bream,Howard A. Young,Jesus Herrera,Jolanta Lissowska,Chiu Chin Yuan,Nathaniel Rothman,George Lanyon,Maureen P. Martin,Joseph F. Fraumeni,Charles S. Rabkin +14 more
TL;DR: It is reported that interleukin-1 gene cluster polymorphisms suspected of enhancing production of interleucine-1-beta are associated with an increased risk of both hypochlorhydria induced by H. pylori and gastric cancer.
Journal ArticleDOI
Cloning of the Gene Containing Mutations that Cause PARK8-Linked Parkinson's Disease
Coro Paisán-Ruiz,Shushant Jain,E. Whitney Evans,William P. Gilks,Javier Fernandez de Simon,Marcel P. van der Brug,Adolfo López de Munain,Silvia Aparicio,Angel Martı́nez Gil,Naheed L. Khan,Janel O. Johnson,Javier Ruiz Martínez,David Nicholl,Itxaso Marti Carrera,Amets Saénz Peňa,Rohan de Silva,Andrew J. Lees,Jose Felix Marti-Masso,Jordi Pérez-Tur,Nicholas W. Wood,Andrew B. Singleton +20 more
TL;DR: The cloning of a novel gene that contains missense mutations segregating with PARK8-linked PD in five families from England and Spain is described and this protein is named dardarin, derived from the Basque word dardara, meaning tremor, because of the tremor observed in PD.
Journal ArticleDOI
Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase
Hideki Shimura,Nobutaka Hattori,Shin-ichiro Kubo,Yoshikuni Mizuno,Shuichi Asakawa,Shinsei Minoshima,Nobuyoshi Shimizu,Kazuhiro Iwai,Tomoki Chiba,Keiji Tanaka,Toshiaki Suzuki +10 more
TL;DR: The findings indicate that accumulation of proteins that have yet to be identified causes a selective neural cell death without formation of Lewy bodies, and should enhance the exploration of the molecular mechanisms of neurodegeneration in Parkinson disease as well as in other Neurodegenerative diseases that are characterized by involvement of abnormal protein ubiquitination.
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Journal ArticleDOI
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Journal ArticleDOI
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Journal ArticleDOI
Linkage of a prion protein missense variant to Gerstmann–Sträussler syndrome
Karen Hsiao,Harry F. Baker,Timothy J. Crow,Mark Poulter,Frank Owen,Joseph D. Terwilliger,David Westaway,Jurg Ott,Jurg Ott,Stanley B. Prusiner +9 more
TL;DR: It is shown here that PrP codon 102 is linked to the putative gene for the syndrome in two pedigrees, providing the best evidence to date that this familial condition is inherited despite also being infectious, and that substitution of leucine for proline at PrPcodon 102 may lead to the development of Gerstmann–Sträussler syndrome.
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