- 作者：Dorota Hoffman-Zacharska ; Dariusz Koziorowski ; Owen A. Ross ; Micha艂 Milewski ; Jaros艂aw Pozna艅ski ; Marta Jurek ; Zbigniew K. Wszolek ; Alex ; ra Soto-Ortolaza ; Jaros艂aw S艂awek ; Piotr Janik ; Zygmunt Jamrozik ; Anna Potulska-Chromik ; Barbara Jasi艅ska-Myga ; Grzegorz Opala ; Anna Krygowska-Wajs ; Krzysztof Czy偶ewski ; Dennis W. Dickson ; Jerzy Bal ; Andrzej Friedman
- 关键词：伪-Synuclein ; SNCA gene ; Parkinson's disease ; Genetic etiology ; Missense mutations
- 刊名：Parkinsonism and Related Disorders
- 出版年：November, 2013
- 年：2013
- 卷：19
- 期：11
- 页码：1057-1060
- 全文大小：459 K
Objective
Mutations in the 伪-synuclein-encoding gene SNCA are considered as a rare cause of Parkinson's disease (PD). Our objective was to examine the frequency of the SNCA point mutations among PD patients of Polish origin.Methods
Detection of the known SNCA point mutations A30P (c.88G>C), E46K (c.136G>A) and A53T (c.157A>T) was performed either using the Sequenom MassArray iPLEX platform or by direct sequencing of the SNCA exons 2 and 3. As the two novel substitutions A18T (c.52G>A) and A29S (c.85G>T) were identified, their frequency in a control population of Polish origin was assessed and in silico analysis performed to investigate the potential impact on protein structure and function.
Results
We did not observe the previously reported point mutations in the SNCA gene in our 629 PD patients; however, two novel potentially pathogenic substitutions A18T and A29S were identified. Each variant was observed in a single patient presenting with a typical late-onset sporadic PD phenotype. Although neither variant was observed in control subjects and in silico protein analysis predicts a damaging effect for A18T and pA29S substitutions, the lack of family history brings into question the true pathogenicity of these rare variants.
Conclusions
Larger population based studies are needed to determine the pathogenicity of the A18T and A29S substitutions. Our findings highlight the possible role of rare variants contributing to disease risk and may support further screening of the SNCA gene in sporadic PD patients from different populations.