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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
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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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Citations
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Journal ArticleDOI

Nrf2/ARE Pathway as a Therapeutic Target for the Treatment of Parkinson Diseases.

TL;DR: The Nrf2/ARE signaling cascade is an optimal target for drugs that could support the mitochondrial quality control, which, in combination with antioxidant protection, can significantly slow down the pathogenesis of PD.
Journal ArticleDOI

Advances in the Research of Risk Factors and Prodromal Biomarkers of Parkinson's Disease.

TL;DR: The exploration of risk factors and premotor biomarkers is not only crucial to the early diagnosis of PD but is also helpful in the development of effective neuroprotection and health care strategies for appropriate populations at risk for PD.
Journal ArticleDOI

Non-human primate models of PD to test novel therapies

TL;DR: Non-human primate models of Parkinson disease show many similarities with the human disease and have been useful to seek new drug targets, since they reproduce motor complications observed in parkinsonian patients as reviewed here.
Journal ArticleDOI

Dopamine D2 receptor-mediated neuroprotection in a G2019S Lrrk2 genetic model of Parkinson’s disease

TL;DR: It is suggested that the G2019S-Lrrk2 mutation is a predisposing factor for enhanced striatal susceptibility to mitochondrial dysfunction induced by exposure to mitochondrial environmental toxins and that the D2 receptor stimulation is neuroprotective on mitochondrial function, via the inhibition of cAMP/PKA intracellular pathway.
Journal ArticleDOI

Centrality of Early Synaptopathy in Parkinson’s Disease

TL;DR: A brief survey of some relevant cellular mechanisms, including autophagic–lysosomal dysfunction, endoplasmic reticulum stress, and mitochondrial impairment, with the main aim to focus on their potential convergent roles in determining early alterations at the synaptic level.
References
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Journal ArticleDOI

Mutation in the α-synuclein gene identified in families with Parkinson's disease

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

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

Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17

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
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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.