Biomedical Research Foundation Academy Of AthensAcademy Of Athens
Research Highlights :A Novel SNCA A30G Mutation Causes Familial Parkinson's Disease


Leonidas Stefanis and colleagues recently published a paper in Movement Disorders


The p.A53T mutation in the SNCA gene, encoding for alpha-synuclein, was the first genetic defect to be linked to Parkinson’s Disease in certain rare families of Italian and Greek origin, more than 20 years ago, and this has led to an explosion of studies linking the aberrant function of alpha-synuclein to the disease.  Collectively, these studies point to the central role of alpha-synuclein in the pathogenesis not only of familial, but also of the more common sporadic disease.  Yet, to date, the exact aberrant function of alpha-synuclein  has not been deciphered. That is why the identification of additional genetic variants or mutations in the SNCA gene always generates a lot of interest, as it can inform its link to Parkinson’s Disease, the second most common neurodegenerative disease.

In this new study, the Stefanis laboratory at BRFAA, together with colleagues at the University of Athens and the laboratories of Thomas Gasser in Tubingen and Markus Zweckstetter in Gottingen, identified a novel point mutation, p.A30G, linked to an autosomal dominant form of Parkinson’s disease in 3 seemingly unrelated Greek families.  All three families seem to share a common genetic structure around the gene, suggesting that they may distantly be related and that the mutation arose as a “founder effect” in the distant past.  More importantly, structural studies of the identified mutant form point to distinct properties conferred by the mutation, including reduced binding to membranes, and enhanced propensity to aggregate, suggesting a “double hit” mechanism of pathogenicity.

This study thus illuminates in a novel fashion, aspects of alpha-synuclein pathogenicity in the context of Parkinson’s Disease, while it also provides another mutation, apart from p. A53T, to screen for in Parkinson’s Disease in Greece.

In the appropriate context of familial disease with a relatively early age of onset and evidence of significant cognitive deterioration, it appears that this mutation should be sought after in patients of Greek origin, thus enriching the palate of Mendelian forms of Parkinson’s Disease in the Greek population.



A Novel SNCA A30G Mutation Causes Familial Parkinson's Disease.
Liu H, Koros C, Strohäker T, Schulte C, Bozi M, Varvaresos S, Ibáñez de Opakua A, Simitsi AM, Bougea A, Voumvourakis K, Maniati M, Papageorgiou SG, Hauser AK, Becker S, Zweckstetter M, Stefanis L, Gasser T.
Mov Disord. 2021 Feb 22. doi: 10.1002/mds.28534. Online ahead of print.