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Monogenic Parkinson's disease and parkinsonism: Clinical phenotypes and frequencies of known mutations.

Andreas Puschmann
- 01 Apr 2013 - 
- Vol. 19, Iss: 4, pp 407-415
TLDR
Clinical features of diseases caused by mutations in SNCA cause cognitive or psychiatric symptoms, parkinsonism, dysautonomia and myoclonus with widespread alpha-synuclein pathology in the central and peripheral nervous system.
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This article is published in Parkinsonism & Related Disorders.The article was published on 2013-04-01 and is currently open access. It has received 211 citations till now. The article focuses on the topics: Parkinsonism & Parkin.

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Journal ArticleDOI

Oxidative stress, mitochondrial damage and neurodegenerative diseases

TL;DR: The contribution of oxidative stress and mitochondrial damage to the onset of neurodegenerative eases is summarized and strategies to modify mitochondrial dysfunction that may be attractive therapeutic interventions for the treatment of various neurodegnerative diseases are discussed.
Journal ArticleDOI

Oxidative stress and Parkinson’s disease

TL;DR: A mini review of the classical pathways involving these mechanisms of neurodegeneration, the biochemical and molecular events that mediate or regulate DA neuronal vulnerability, and the role of PD-related gene products in modulating cellular responses to oxidative stress in the course of the Neurodegenerative process are given.
Journal ArticleDOI

Parkinson’s disease: animal models and dopaminergic cell vulnerability

TL;DR: A summary of current knowledge about the different in vivo models of PD that are used in relation to the vulnerability of the dopaminergic neurons in the midbrain in the pathogenesis of PD is provided.
Journal ArticleDOI

SOD2 in mitochondrial dysfunction and neurodegeneration.

TL;DR: SOD2's potential involvement in the progression of neurodegenerative diseases such as stroke and Alzheimer and Parkinson diseases, as well as its potential role in "normal" age-related cognitive decline are reviewed.
Journal ArticleDOI

α-Synuclein misfolding and aggregation: Implications in Parkinson's disease pathogenesis.

TL;DR: The structural and functional aspects of α-Syn and role of potential factors that may contribute to the underlying mechanism of synucleinopathies are focused on to identify novel targets and develop specific therapeutic strategies to combat Parkinson's and other protein aggregation related neurodegenerative diseases.
References
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Journal ArticleDOI

LRRK2 G2019S as a cause of Parkinson's disease in Ashkenazi Jews.

TL;DR: To the Editor: Most cases of Parkinson's disease are considered sporadic and idiopathic, although there is evidence of familial aggregation, and several monogenic forms have been identified.
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Frequently Asked Questions (12)
Q1. What are the contributions mentioned in the paper "Monogenic parkinson’s disease and parkinsonism: clinical phenotypes and frequencies of known mutations" ?

This review summarizes the clinical features of diseases caused by mutations in 

More than 100 different parkin mutations have been reported from PD patients, including copy number variations (deletions, insertions, multiplications), missense and truncating mutations [101]. 

In a recently published international multicenter study, only 49 of 8,371 (0.58%) PD patients of European and Asian origin carried a LRRK2 G2019S mutation [44]. 

Other studies found homozygous or compound heterozygous parkin mutations in a lower percentage of patients with early onset-PD (before 40 or 45 years), ranging from 8.2% in Italy, 2.7% in Korea, 2.5% in Poland, to 1.4% in Australia [8, 98-100]. 

In rare patients, parkinsonism has been the presenting or predominant clinical manifestation of GRN mutation [77], but mutations in MAPT or GRN are not considered a major cause of familial parkinsonism, especially in the absence of other clinical signs and symptoms. 

In families with recessive patterns of inheritance, cosegregation analysis is often limited to a few siblings, but siblings have a 25% chance probability to have inherited the identical allele. 

12Puschmann: Review monogenic PDFeatures common to patients with parkin mutations and PD, aside from young or very young age at onset, are probably a good and lasting effect of levodopa, albeit with the occurrence of dyskinesias during the disease course, and a lower risk for non-motor symptoms such as cognitive decline and dysautonomia [102]. 

The phenotypes caused by mutations in SNCA or the recessive PD genes (parkin, PINK1, DJ1) represent characteristic subtypes of PD. 

Given the prevalence of D620N of 0.14% among PD patients in the two initial studies and of 0.4% in the multicentre study [58], and the fact that replication studies in Belgium [61] or China [62] have not identified additional cases, this mutation is rare. 

Late-onset PD was reported in the Austrian family, one member had only developed depression and tremor with a pathological DATscan indicating incipient PD [55]. 

Genetic testing can today be offered to a subset of patients with unusually young onset, dominant inheritance, and/or a clinical phenotype suggesting a defined monogenic form of parkinsonism. 

Carriers of mutations in the other genes may develop parkinsonism with or without additional symptoms, but rarely a disease resembling PD.