Journal ArticleDOI
Clinical heterogeneity of α‐synuclein gene duplication in Parkinson's disease
Kenya Nishioka,Shin Hayashi,Matthew J. Farrer,Andrew B. Singleton,Hiroyo Yoshino,Hisamasa Imai,Toshiaki Kitami,Kenichi Sato,Ryu Kuroda,Hiroyuki Tomiyama,Koichi Mizoguchi,Miho Murata,Tatsushi Toda,Issei Imoto,Johji Inazawa,Yoshikuni Mizuno,Nobutaka Hattori +16 more
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TLDR
The objective of this study was to assess the frequency of SNCA multiplications among autosomal dominant hereditary Parkinson's disease (ADPD) patients.Abstract:
Objective
Recently, genomic multiplications of α-synuclein gene (SNCA) have been reported to cause hereditary early-onset parkinsonism. The objective of this study was to assess the frequency of SNCA multiplications among autosomal dominant hereditary Parkinson's disease (ADPD).
Methods
We screened 113 ADPD probands and 200 sporadic PD cases by quantitative polymerase chain reaction and confirmed SNCA multiplications by flurorescence in situ hybridization (FISH) and comparative genomic hybridization array.
Results
Two families (two patients from Family A and one from Family B) with SNCA duplication were identified among ADPD patients. Even though they had the same SNCA duplication, one patient had dementia. Because there was exactly the same difference between the regions originated from each patient, the finding suggests that the phenotype of SNCA multiplication may be also influenced by the range of duplication region. We also detected asymptomatic carriers in the families of both patients. Interestingly, the penetrance ratio was 33.3% (2/6) in one kindred, indicating that the ratio was very much lower than expected.
Interpretation
These two newly identified Japanese patients with SNCA duplication and the five previously identified American and European families with SNCA triplication or duplication mutations indicate that the incidence of SNCA multiplication may be more frequent than previously estimated. Ann Neurol 2006read more
Citations
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Journal ArticleDOI
Genetics of Parkinson’s Disease
Christine Klein,Ana Westenberger +1 more
TL;DR: This article will review familial forms of PD, basic genetic principles of inheritance (and their exceptions in PD), followed by current methods for the identification of PD genes and risk factors, and implications for genetic testing.
Journal ArticleDOI
Parkinson's disease: from monogenic forms to genetic susceptibility factors
Suzanne Lesage,Alexis Brice +1 more
TL;DR: Genome-wide associations and re-sequencing projects, together with gene-environment interaction studies, are expected to further define the causal role of genetic determinants in the pathogenesis of PD, and improve prevention and treatment.
Journal ArticleDOI
Epidemiology and etiology of Parkinson’s disease: a review of the evidence
Karin Wirdefeldt,Hans-Olov Adami,Hans-Olov Adami,Philip A. Cole,Dimitrios Trichopoulos,Jack S. Mandel +5 more
TL;DR: Studies that assessed possible shared etiological components between PD and other diseases show that REM sleep behavior disorder and mental illness increase PD risk and that PD patients have lower cancer risk, but methodological concerns exist.
Journal ArticleDOI
A DNA Replication Mechanism for Generating Nonrecurrent Rearrangements Associated with Genomic Disorders
TL;DR: Analysis of junction sequences in PMD patients confirms the occurrence of simple tandem PLP1 duplications but also uncovers evidence for sequence complexity at some junctions, consistent with a replication-based mechanism that is termed FoSTeS, for replication Fork Stalling and Template Switching.
Book ChapterDOI
Etiology and Pathogenesis of Parkinson’s Disease
Taku Hatano,Nobutaka Hattori +1 more
TL;DR: Genetic factors clearly contribute to the pathogenesis of Parkinson’s disease, and many studies have shed light on their implication in, not only monogenic, but also sporadic forms of PD.
References
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Journal ArticleDOI
Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases.
TL;DR: The pathological findings in 100 patients diagnosed prospectively by a group of consultant neurologists as having idiopathic Parkinson's disease are reported, and these observations call into question current concepts of Parkinson's Disease as a single distinct morbid entity.
Journal ArticleDOI
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
Alpha-synuclein in Lewy bodies.
Maria Grazia Spillantini,Marie L. Schmidt,Virginia M.-Y. Lee,John Q. Trojanowski,Ross Jakes,Michel Goedert +5 more
TL;DR: Strong staining of Lewy bodies from idiopathic Parkinson's disease with antibodies for α-synuclein, a presynaptic protein of unknown function which is mutated in some familial cases of the disease, indicates that the LewY bodies from these two diseases may have identical compositions.
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.
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