肌萎缩侧索硬化
错义突变
单核苷酸多态性
发病机制
遗传学
疾病
LRRK2
单倍型
帕金森病
额颞叶变性
生物
SNP公司
单倍率不足
遗传关联
突变
医学
失智症
病理
基因
免疫学
等位基因
基因型
痴呆
表型
作者
Karen Nuytemans,P. Pals,Kristel Sleegers,Sebastiaan Engelborghs,Ellen Corsmit,Karin Peeters,Barbara Pickut,Maria Mattheijssens,Patrick Cras,Peter P. De Deyn,Jessie Theuns,Christine Van Broeckhoven
出处
期刊:Neurology
[Ovid Technologies (Wolters Kluwer)]
日期:2008-10-06
卷期号:71 (15): 1147-1151
被引量:22
标识
DOI:10.1212/01.wnl.0000327563.10320.2b
摘要
Background: Different loss-of-function mutations were identified underlying PGRN haploinsufficiency in patients with frontotemporal lobar degeneration. PGRN mutations were also identified in other neurodegenerative brain diseases such as amyotrophic lateral sclerosis and Alzheimer disease, though their biologic contribution to these diseases remains elusive. Because of its apparent role in neuronal survival, we argued that PGRN might also contribute to Parkinson disease (PD) pathogenesis. Methods: We screened PGRN exons for mutations in 255 patients with PD and 459 control individuals by direct genomic sequencing. Genetic association of PGRN with risk for PD was assessed using single nucleotide polymorphisms (SNPs) across the gene. Results: In patients we identified four missense mutations of which p.Asp33Glu and p.Arg514Met were absent in control individuals. Single SNP and haplotype analyses did not detect significant associations with PD. Conclusions: Our results do not support a major role for PGRN in the genetic etiology of Parkinson disease (PD). At this stage and in the absence of functional data, it remains unclear whether p.Asp33Glu and p.Arg514Met are biologically relevant to PD pathogenesis in the mutation carriers.
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