Mutation Analysis of the Genes Associated with Parkinson's Disease in a Finnish Cohort of Early-Onset Dementia

被引:0
作者
Luukkainen, Laura [1 ,2 ,3 ]
Huttula, Samuli [1 ,3 ]
Vayrynen, Henri [1 ,3 ]
Helisalmi, Seppo [4 ]
Kytovuori, Laura [1 ,3 ]
Haapasalo, Annakaisa [5 ]
Hiltunen, Mikko [6 ]
Remes, Anne M. [1 ,3 ]
Kruger, Johanna [1 ,3 ]
机构
[1] Univ Oulu, Res Unit Clin Neurosci, Neurol, Oulu, Finland
[2] Univ Oulu, Unit Canc & Translat Res, Pathol, Oulu, Finland
[3] Oulu Univ Hosp, MRC, Oulu, Finland
[4] Univ Eastern Finland, Inst Clin Med Neurol, Kuopio, Finland
[5] Univ Eastern Finland, AI Virtanen Inst Mol Sci, Kuopio, Finland
[6] Univ Eastern Finland, Inst Biomed, Kuopio, Finland
基金
芬兰科学院;
关键词
Alzheimer's disease; dementia; dementia with Lewy bodies; frontotemporal dementia; frontotemporal lobar degeneration; gene; mutation; neurodegenerative disease; Parkinson's disease; single nucleotide polymorphism; ALZHEIMERS-DISEASE; LEWY BODIES; LRRK2; GENE; DIAGNOSIS; GLUCOCEREBROSIDASE; POLYMORPHISMS; PREVALENCE; CRITERIA; VARIANT;
D O I
10.3233/JAD-200069
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Background: Alzheimer's disease, frontotemporal lobar degeneration, dementia with Lewy bodies, and Parkinson's disease (PD) overlap in clinical characteristics, neuropathology, and genetics. Objective: The aim of this study was to evaluate the role of pathogenic mutations and rare variants in genes associated with PD among early-onset dementia (EOD) patients. Methods: Rare non-synonymous variants (MAF < 0.01) in ten genes (SNCA, PARK2, PARK7, LRRK2, PINK1, ATP13A2, UCHL1, HTRA2, GBA, and SNCAIP) and low-frequency (MAF < 0.05) GBA variants were screened using a targeted nextgeneration sequencing panel in a strictly defined cohort of 37 early-onset (age at onset (AAO) <65 years) dementia patients presenting with atypical features (e.g., myoclonia or spasticity), rapidly progressive course of the disease or with a family history of dementia. The identified variations were further screened in a larger cohort of EOD (n = 279, mean AAO 57, range 36-65) patients. Results: No pathogenic mutations were found, but we identified seven possible risk variants for neurodegeneration (LRRK2 p.Arg793Met, PARK2 p.Ala82Glu, SNCAIP p.Arg240Gln, SNCAIP p.Phe369Leu, GBA p.Asn409Ser, GBA p.Glu365Lys, GBA p.Thr408Met). Discussion: Altogether, the frequency of these variants was two times higher in the first selected cohort compared to the whole cohort. This suggests that specific rare variants in the genes associated with PD might play a role also especially in familial EOD.
引用
收藏
页码:955 / 965
页数:11
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