Pasanen Petra, Palin Eino, Pohjolan-Pirhonen Risto, Pöyhönen Minna, Rinne Juha O, Päivärinta Markku, Martikainen Mika H, Kaasinen Valtteri, Hietala Marja, Gardberg Maria, Saukkonen Anna Maija, Eerola-Rautio Johanna, Kaakkola Seppo, Lyytinen Jukka, Tienari Pentti J, Paetau Anders, Suomalainen Anu, Myllykangas Liisa
Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland; Department of Medical Genetics, Tyks Microbiology and Genetics, Turku University Hospital, Turku, Finland.
Molecular Neurology, Research Programs Unit, University of Helsinki, Helsinki, Finland.
Neurobiol Aging. 2017 Feb;50:168.e5-168.e8. doi: 10.1016/j.neurobiolaging.2016.10.014. Epub 2016 Oct 19.
Mutations in SNCA are rare causes of familial Parkinson's disease (PD). We have previously described a novel p.Ala53Glu mutation in 2 Finnish families. To assess this mutation's frequency among Finnish PD patients, we screened 110 PD patients (mean age-of-onset 60 years) from Western Finland by Sanger sequencing of the third coding exon of SNCA. In addition, a sample of 47 PD subjects (mean age-of-onset 53 years) originating from Southern and Eastern Finland were studied using next-generation sequencing covering SNCA. Only one new individual with the p.Ala53Glu mutation was identified, confirming that this mutation is a rare cause of PD in the Finnish population. To search for a possible common origin of the p.Ala53Glu mutation, haplotype analysis was conducted in 2 families and in a patient from a third family (6 affected subjects) using both STR markers and a genome-wide SNP array. The results show that patients with the p.Ala53Glu mutation share a haplotype spanning a minimum of 5.7 Mb suggesting a common founder.
SNCA基因突变是家族性帕金森病（PD）的罕见病因。我们之前在2个芬兰家族中描述了一种新的p.Ala53Glu突变。为评估该突变在芬兰PD患者中的频率，我们通过对SNCA第三个编码外显子进行桑格测序，筛查了来自芬兰西部的110例PD患者（平均发病年龄60岁）。此外，我们使用覆盖SNCA的新一代测序技术，对来自芬兰南部和东部的47例PD受试者（平均发病年龄53岁）样本进行了研究。仅发现1例携带p.Ala53Glu突变的新个体，证实该突变在芬兰人群中是PD的罕见病因。为探寻p.Ala53Glu突变可能的共同起源，我们使用STR标记和全基因组SNP阵列，对2个家族以及来自第三个家族的1例患者（6名受累受试者）进行了单倍型分析。结果显示，携带p.Ala53Glu突变的患者共享一个最小跨度为5.7 Mb的单倍型，提示存在一个共同的奠基者。
