RGD Reference Report - Clinicogenetic study of GBA mutations in patients with familial Parkinson's disease. - Rat Genome Database

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

Authors: Li, Yuanzhe  Sekine, Takeshi  Funayama, Manabu  Li, Lin  Yoshino, Hiroyo  Nishioka, Kenya  Tomiyama, Hiroyuki  Hattori, Nobutaka 
Citation: Li Y, etal., Neurobiol Aging. 2014 Apr;35(4):935.e3-8. doi: 10.1016/j.neurobiolaging.2013.09.019. Epub 2013 Oct 12.
RGD ID: 12791016
Pubmed: PMID:24126159   (View Abstract at PubMed)
DOI: DOI:10.1016/j.neurobiolaging.2013.09.019   (Journal Full-text)

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 = 22.9, 95% confidence interval = 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 (123)I-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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Parkinson's disease  IAGP 12791016DNA:mutations:multiple (human)RGD 
Parkinson's disease  ISOGBA1 (Homo sapiens)12791016; 12791016DNA:mutations:multiple (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gba1  (glucosylceramidase beta 1)

Genes (Mus musculus)
Gba1  (glucosylceramidase beta 1)

Genes (Homo sapiens)
GBA1  (glucosylceramidase beta 1)


Additional Information