Genetic basis of Parkinson's disease: inheritance, penetrance, and expression

Schulte, Claudia; Gasser, Thomas

doi:10.2147/tacg.s11639

Cited by 84 publications

(59 citation statements)

References 168 publications

(242 reference statements)

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“…These findings indicate that environmental factors may also play an important role in the development of PD [ 6 ]. Primary PD patients with a distinct familial history represent 10–15% of all PD cases, revealing significant genetic susceptibility and the involvement of familial and genetic factors [ 12 , 13 ]. The vast majority of PD patients have no apparent genetic predisposition, suggesting that the development of PD may be the combined action of environmental factors and genetic susceptibility [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Analysis of Thr12Met and Ala1144Thr Mutations of the ATP13A2 Gene in Parkinson’s Disease Patients in Xinjiang Uygur and Han Ethnic Groups

Zhang

Xia

et al. 2014

Med Sci Monit

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BackgroundIt has been reported that the ATP13A2 gene is one of the most susceptible pathogenic genes of Parkinson’s disease (PD). PARK9 mutations are found in early-onset PD and familial PD patients. Uygur and Han PD patients in the Xinjiang area were recruited as research subjects to study the differences in the Thr12Met and Ala1144Thr loci mutations of the ATP13A2 gene in these PD populations. This study explored the mutations at the Thr12Met and Ala1144Thr gene loci of the ATP13A2 gene in Parkinson’s disease patients in the Uygur and Han populations in the Xinjiang province.Material/MethodsThe polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to analyze the Thr12Met and Ala1144Thr mutations of the ATP13A2 gene in a case-control study of 200 age- and sex- matched Uygur and Han PD patients.ResultsOf the 200 PD patients were studied, 2 from the Han group had a Thr12Met mutation, but Ala1144Thr mutations were not found. Among the Uygur PD patients, no Thr12Met or Ala1144Thr mutations were found.ConclusionsThr12Met and Ala1144Thr mutations of the ATP13A2 gene are rare in the Uygur PD patients in Xinjiang. Overall, the mutation rates of Thr12Met and Ala1144Thr in the Uygur and Han PD patients in the Xinjiang region are low.

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Section: Discussionmentioning

confidence: 99%

Analysis of Thr12Met and Ala1144Thr Mutations of the ATP13A2 Gene in Parkinson’s Disease Patients in Xinjiang Uygur and Han Ethnic Groups

Zhang

Xia

et al. 2014

Med Sci Monit

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“…There have been identified several genes and their mutations associated with EOPD, but new loci are still being identified. Most of these genes are inherited autosomal recessive, for example, PRKN, PINK1, or DJ1, but some of them are associated with the autosomal dominant pattern, for example, SNCA [30].…”

Section: Genetic Risk Factors For Early-onset Parkinson's Diseasementioning

confidence: 99%

“…SNCA (PARK1 and PARK4) gene was the first gene ever identified as causal PD. It is an inherited autosomal dominant pattern and located to chromosome 4q22.1 [30]. SNCA gene encodes ASN, but the functions of its are still not completely understood.…”

Section: Snca Genementioning

confidence: 99%

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Dopamine and Early Onset Parkinson’s Disease

Wize¹,

Kozubski²,

Dorszewska³

2018

Dopamine - Health and Disease

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Parkinson's disease (PD) is divided into early-onset (EOPD) occurring at the age of fewer than 45 years of age and late-onset PD (LOPD) above 45 years of age. EOPD accounts for 5-10% of all the cases with PD. It is thought that occurrence in this age is connected with genetic factors, mutations in e.g. PRKN, PINK1, DJ-1 and changes in proteins it is encoded. The loss of dopaminergic neurons in the nigrostriatal system leads to decreased dopamine (DA) concentrations. Pathogenic PD proteins may affect the DA level. The lower level of DA may be responsible for movement-related symptoms. EOPDs have a slower progression of the disease and a longer disorder duration but tend to develop dyskinesias and motor fluctuations earlier than LOPD. Currently, the diagnosis of PD is based on clinical criteria, supported neuroimaging like MRI or PET. Understanding the pathogenesis of the EOPD may be contributing to improving diagnostics and effectiveness of pharmacotherapy.

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“…Point mutations and multiplications of the α-synuclein (α-SYN) gene, SNCA, cause a rare familial autosomal dominant form of PD [ 2 ]. α-SYN is a small protein of 140 amino acids that is widely expressed in the brain and localizes predominantly to presynaptic terminals [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Nigral overexpression of alpha-synuclein in the absence of parkin enhances alpha-synuclein phosphorylation but does not modulate dopaminergic neurodegeneration

Rompuy

Oliveras-Salvá

Perren

et al. 2015

Mol Neurodegeneration

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BackgroundAlpha-synuclein is a key protein in the pathogenesis of Parkinson’s disease. Mutations in the parkin gene are the most common cause of early-onset autosomal recessive Parkinson’s disease, probably through a loss-of-function mechanism. However, the molecular mechanism by which loss of parkin function leads to the development of the disease and the role of alpha-synuclein in parkin-associated Parkinson’s disease is still not elucidated. Conflicting results were reported about the effect of the absence of parkin on alpha-synuclein-mediated neurotoxicity using a transgenic approach. In this study, we investigated the effect of loss of parkin on alpha-synuclein neuropathology and toxicity in adult rodent brain using viral vectors. Therefore, we overexpressed human wild type alpha-synuclein in the substantia nigra of parkin knockout and wild type mice using two different doses of recombinant adeno-associated viral vectors.ResultsNo difference was observed in nigral dopaminergic cell loss between the parkin knockout mice and wild type mice up to 16 weeks after viral vector injection. However, the level of alpha-synuclein phosphorylated at serine residue 129 in the substantia nigra was significantly increased in the parkin knockout mice compared to the wild type mice while the total expression level of alpha-synuclein was similar in both groups. The increased alpha-synuclein phosphorylation was confirmed in a parkin knockdown cell line.ConclusionsThese findings support a functional relationship between parkin and alpha-synuclein phosphorylation in rodent brain.

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Genetic basis of Parkinson's disease: inheritance, penetrance, and expression

Cited by 84 publications

References 168 publications

Analysis of Thr12Met and Ala1144Thr Mutations of the ATP13A2 Gene in Parkinson’s Disease Patients in Xinjiang Uygur and Han Ethnic Groups

Analysis of Thr12Met and Ala1144Thr Mutations of the ATP13A2 Gene in Parkinson’s Disease Patients in Xinjiang Uygur and Han Ethnic Groups

Dopamine and Early Onset Parkinson’s Disease

Nigral overexpression of alpha-synuclein in the absence of parkin enhances alpha-synuclein phosphorylation but does not modulate dopaminergic neurodegeneration

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