We screened for the p. A53TSNCA mutation a total of 347 cases of Greek origin with parkinsonism and/or dementia, collected over 15 years at the Neurogenetics Unit, Eginition Hospital, University of Athens.
In this study no one of our 85 patients of Serbian origin with young-onset (</= 45 years) dopa-responsive parkinsonism (YOP), previously proved negative forPARK1 and PARK2 mutations, had either spinocerebellar ataxia type 2 (SCA2) or SCA3 mutation.
NMR spectroscopy demonstrates that Parkinsonism-linked mutations greatly perturb specific tertiary interactions essential for the native state of alpha-synuclein.
With the discovery of missense and multiplication mutations in the alpha-synuclein gene (SNCA) in familial parkinsonism, Lewy inclusions were found to stain intensely with antibodies raised against the protein.
Since the discovery in 1997 of the first heritable form of parkinsonism that could be linked to a mutation in a single gene, SNCA, many more genetic leads have followed (Parkin, DJ-1, PINK1, LRRK2, to name a few); these have provided us with many molecular clues to better explore the etiology of parkinsonism and have led to the dismantling of many previously held dogmas about Parkinson disease (PD).
These results indicated that the parkinsonism of the Sagamihara family seems not to be due to previously identified point mutations of alpha-synuclein, tau, or UCH-L1, or to exon deletion of parkin.
An analysis of 43 tagging single nucleotide polymorphisms across the SNCA locus shows 2 distinct association profiles for symptoms of parkinsonism and/or dementia, respectively, toward the 3' or the 5' of the SNCA gene.
The alpha-synuclein gene (SNCA) multiplication causes autosomal dominant Parkinson Disease (PD): triplication is associated with early-onset rapidly progressing parkinsonism with a strong likelihood of developing dementia, while duplication is associated with a less severe phenotype similar to idiopathic PD.
Recent molecular biology research on neurodegenerative diseases, including parkinsonisms, has identified mutations in the genes that code for the proteins alpha-synuclein and tau, which have been used to classify them into synucleinopathies and tauopathies.
The SNCA duplication case presented with a clinical phenotype of frontotemporal dementia with marked behavioural changes, pyramidal signs, postural hypotension and transiently levodopa responsive parkinsonism.
We hypothesize that the former pediatric disease, as well as the parkinsonism and dementia phenotypes, are associated with duplications, triplications and possibly higher-order multiplications of the alpha-synuclein (SNCA) gene.
Herein we characterize five families with parkinsonism that have been identified to harbor multiplication of the chromosomal 4q21 locus containing the alpha-synuclein gene (SNCA).
Alpha-synuclein (SNCA) is a major risk gene for Parkinson's disease (PD), and increased SNCA gene dosage results in a parkinsonian syndrome in affected families.
Mutations and multiplications of alpha-synuclein (α-syn) cause familial PD, and chronic manganese (Mn) exposure can produce an encephalopathy with signs of parkinsonism.
These findings prompted us to screen for multiplication of the SNCA locus in nine families in whom parkinsonism segregates as an autosomal dominant trait.
Pathologically confirmed Lewy body disease clinically characterized by progressive parkinsonism and cognitive dysfunction is caused by SNCA duplication.
Particularly triplication, but also duplication, of the SNCA is associated with early-onset rapidly progressing parkinsonism with increased risk of cognitive impairment.
Pathologically confirmed Lewy body disease clinically characterized by progressive parkinsonism and cognitive dysfunction is caused by SNCA duplication.