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.
To report a novel family carrying a heterozygous 6.4 Mb duplication of the SNCA locus with an atypical clinical presentation strongly reminiscent of frontotemporal dementia and late-onset pallidopyramidal syndromes and study phenotype-genotype correlations in SNCA locus duplications.
Mutations in the tau gene in familial forms of frontotemporal dementia and in the alpha-synuclein gene in familial cases of Parkinson's disease have provided causal links between the dysfunction of these proteins and neurodegeneration.
Importantly, the discovery of mutations in the tau gene in familial forms of frontotemporal dementia and of mutations in the alpha-synuclein gene in familial forms of Parkinson's disease has established that dysfunction of tau protein and alpha-synuclein can cause neurodegeneration.
Over the past year, mutations in the genes for tau and alpha-synuclein have been identified as the genetic causes of some familial forms of frontotemporal dementia and Parkinson's disease, respectively.