We hypothesized that specific mutations in the β-glucocerebrosidase gene (GBA) causing neuropathic Gaucher's disease (GD) in homozygotes lead to aggressive cognitive decline in heterozygous Parkinson's disease (PD) patients, whereas non-neuropathic GD mutations confer intermediate progression rates.
Recent evidence suggests that glucosidase beta acid (GBA) mutations predispose Parkinson's disease (PD) patients to a greater burden of cognitive impairment and non-motor symptoms.
In addition to the identification of the causes of monogenic forms of PD, significant progress has been made in defining genetic risk loci for PD; we discuss these here, including both risk variants at LRRK2 and GBA, in addition to discussing the results of recent genome-wide association studies and their implications for PD.
The key DBS efficacy studies were performed in PD patients with unknown genotypes; however, given the estimated monogenic mutation prevalence of approximately 5-10%, most commonly LRRK2, PRKN, PINK1 and SNCA, and risk-increasing genetic factors such as GBA, proper characterization is becoming increasingly relevant.
The discovery that E326K negatively impacts cognitive performance approximately doubles the proportion of PD patients we now recognize are at risk for more severe GBA-related cognitive deficits.
We conducted a longitudinal analysis of Parkinson's disease (PD) patients carrying mutations in the GBA gene to better characterize genotype-phenotype correlations.
We found two patients in one familial PD (FPD) family (1.5%) and two sporadic PD patients (0.5%) with expanded CAG repeats in the ATXN2 locus, four patients in two FPD families (3%) and another three sporadic PD patients (0.8%) in the MJD1 locus.
A functional SNP (rs9347683) in the promoter region of the parkin gene had been implicated as a risk factor in older Parkinson's disease (PD) patients.
Mutation screening of PARK2 was performed in 225 Serbian PD patients (143 males and 82 females) with disease onset before 50 years and/or positive family history with apparent AR inheritance.
Moreover, Miro1 turnover on damaged mitochondria is altered in Parkinson disease (PD) patient-derived fibroblasts containing a pathogenic mutation in the PARK2 gene (encoding Parkin).
The identification of copy number variations in the Parkin gene in healthy control individuals suggests no major role of these variations in late onset Parkinson's disease.
The percentage of TH(+) neurons was decreased in Parkinson's disease (PD) patient-derived neurons carrying various mutations in PARK2 compared with an age-matched control subject.
Interestingly, axonal alpha-synuclein deposits were absent in epicardial tissue of the PARK2 mutation carrier while they were present in the two PD patients.