Glucocerebrosidase mutations p.L444P and p.N370S are not associated with multisystem atrophy, progressive supranuclear palsy and corticobasal degeneration in Polish patients

Excerpt

Recently, mutations in the GBA gene coding for lysosomal beta-glucocerebrosidase have been found as a risk factor for Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB) [1‐3]. These mutations seem to participate in the formation of Lewy bodies. PD and DLB have been classified as synucleinopathies; the third most common synucleinopathy are multisystem atrophies (MSA), which may share with PD and DLB at least part of the molecular pathogenesis. The incidence of mutations in the GBA gene in PD patients is variable and related to different populations studied, methods of DNA testing (sequencing versus looking for the most common mutations only), and different control groups. Lewy bodies were also found in some patients with tauopathies like Progressive Supranuclear Palsy (PSP) and corticobasal degeneration (CBD) [4‐6]. Thus lysosomal dysfunction caused by GBA mutations may alter or disrupt the processing of the alpha- or beta-synuclein [4]. To identify mutations in the GBA gene, genomic DNA was extracted from the white blood cells by standard techniques. A screening for mutations, p.L444P and p.N370S was performed in a group of 66 MSA patients (MSA-P = 34) and (MSA-C = 31), 34 PSP patients and in five cases of CBD. The patients were diagnosed at two movement disordered centers according to clinical criteria and the level of diagnosis (possible and probable) is shown in Table 1. PCR-RFLP methods were used as described earlier. Our results were compared to incidence of GBA mutations in other European populations and in PD/DLB patients [1‐3]. …