Association between parkinson's disease and mutations of glucocerebrosidase gene on Crete
Συσχετισμός μεταξύ της ασθένειας του Πάρκισον και μεταλλάξεων του γονιδίου της γλουκοσερεμπροσιδάσης στην Κρήτη
Homozygous mutations in the gene of GBA, lead to Gaucher disease (GD), a lysosomal storage disorder, whereas heterozygous mutations are considered to be a major risk factor for the development of Parkinson’s disease (PD), even though the molecular mechanism of this association remains elusive.
In this study we aimed to assess the possible involvement of GBA mutations in Cretan PD patients and to evaluate clinically the GBA-positive PD patients. We assessed the frequency of the two more common mutations in GD, N370S and L444P, in 243 PD patients and in a control group of 134 healthy individuals. We identified 6 GBA-carriers in PD patients and 2 in the controls, with a frequency of 2.5% versus 1.5% respectively that was not statistically significant (p = 0.797). N370S mutation was found only in one PD patient (0.6%), while L444P was found in 5 PD patients (2.8%) and in 2 controls (1.6%). Subsequently, we compared clinical and demographic data of GBA-positive PD patients with PD patients cohort. GBA-carriers displayed an earlier onset of PD than non-carriers. Moreover, an increased prevalence of dementia, psychosis, depression and hyperkinesias in GBA-carriers was observed. The clinical phenotype of the GBA-carriers was heterogeneous. Specifically the L44P mutation was associated with typical idiopathic PD or parkinsonism with atypical features, such as Pisa syndrome, pyramidal signs and vertical ophthalmoplegia.
In conclusion, GBA gene mutations are associated with PD in the Cretan population. GBA-carriers were found to present both a typical and an atypical parkinsonian phenotype.