SNCA mutation p.Ala53Glu is derived from a common founder in the Finnish population

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• 作者：Petra Pasanen^a ; ^b ; Eino Palin^c ; Risto Pohjolan-Pirhonen^c ; Minna Pö ; yhö ; nen^d ; ^e ; Juha O. Rinne^f ; ^g ; Markku P&auml ; iv&auml ; rinta^h ; Mika H. Martikainen^g ; Valtteri Kaasinen^f ; ^g ; ⁱ ; Marja Hietala^j ; Maria Gardberg^k ; Anna Maija Saukkonen^l ; Johanna Eerola-Rautio^c ; ^m ; Seppo Kaakkola^m ; Jukka Lyytinen^m ; Pentti J. Tienari^c ; ^m ; Anders Paetauⁿ ; Anu Suomalainen^c ; Liisa Myllykangasⁿ ; ^{liisa.myllykangas@helsinki.fi}
• 关键词：SNCA ; A53E ; Haplotype ; Founder effect
• 刊名：Neurobiology of Aging
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：50
• 期：Complete
• 页码：168.e5-168.e8
• 全文大小：505 K
• 卷排序：50

文摘

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.