Clinicogenetic study of GBA mutations in patients with familial Parkinson's disease

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• 作者：Yuanzhe Li ; Takeshi Sekine ; Manabu Funayama ; Lin Li ; Hiroyo Yoshino ; Kenya Nishioka ; Hiroyuki Tomiyama ; Nobutaka Hattori
• 关键词：Parkinson's disease/Parkinsonism ; GBA ; Dementia ; Gaucher disease
• 刊名：Neurobiology of Aging
• 出版年：April, 2014
• 年：2014
• 卷：35
• 期：4
• 页码：935.e3-935.e8
• 全文大小：523 K

文摘

The glucocerebrosidase gene (GBA) is a known risk factor of Parkinson's disease (PD). We sequenced entire coding exons and exon/intron boundaries of GBA in 147 Japanese familial PD (FPD) patients from 144 families and 100 unrelated control subjects. Twenty-seven of 144 (18.8%) of index patients were heterozygous for known Gaucher disease mutations, suggesting that GBA heterozygous mutations are strongly associated with FPD (odds ratio聽= 22.9, 95% confidence interval聽= 3.1-171.2). The frequency was significantly higher in autosomal dominant PD (ADPD) compared with autosomal recessive PD. According to clinical assessments, PD patients with GBA mutations exhibited typical manifestations of PD or dementia with Lewy bodies (DLB), such as L-dopa responsive parkinsonism with psychiatric problems and/or cognitive decline. Interestingly, they also presented with reduced myocardial ¹²³I-metaiodobenzylguanidine uptake. Our findings suggest that heterozygous GBA mutations are strong risk factors in FPD, especially for autosomal dominant PD. Some patients with GBA heterozygous mutations develop clinical features of DLB. We speculate that GBA dysfunction may promote Lewy body formation, resulting in more severe PD or DLB phenotypes that are inherited in families.