GBA Mutation Analysis in Turkish Parkinson’s Disease Patients: Comparison of Clinical and Cognitive Performance

Background: Recent studies have established a substantial relationship between GBA gene and Parkinson’s Disease (PD). Mutations in the GBA play an important role in the pathogenesis of PD.

Methods: 33 young onset and 38 idiopathic PD patients and 76 healthy controls were screened with real time PCR for 11 GBA mutations (N370S, L444P, D409H, 84insGG, IVS2+1G>A, V394L, IVS10-1 G>A, IVS10-4 C>T, R120W, V460V and R496H). Leukocyte GBA expression levels were also investigated. All patients underwent a comprehensive assessment based on the Unified Parkinson’s Disease Rating Scale (UPDRS), H&Y scale, Hamilton’s Depression Scale (HDS), Non-Motor Symptom Questionnaire, Mini Mental State Examination (MMSE) and Addenbrooke’s Cognitive Examination (ACE-R).

Results: Mutation screening showed that 15.5% of PD patients and 0% of controls had GBA mutations (p=0,000). The most common GBA mutations were R496H and L444P mutations. Leukocyte GBA expression was significantly lower in patients with respect to the control (p=0,04). There was no difference in terms of clinical manifestations between mutation positive and negative PD patients.

Conclusions: This study is the first study to investigate the relationship between Parkinson’s disease and GBA mutations in Turkey. The results show that R496H mutation is frequent (14%) among Turkish PD patients. This mutation is related with neither early onset nor clinical manifestations. Regardless from mutation presence most of the PD patients (84.5 %) have cognitive impairment when tested with ACE-R.

Keywords:Parkinson’s disease; Glucocerebrosidase; GBA mutation; ACE-R