Objective: We investigated the frequency of GBA mutations in the Korean patients with early-onset Parkinson’s disease (PD).

Background: Glucocerebrosidase (GBA) mutations are associated with increased risk and earlier onset of PD. The frequency of GBA mutations varies between populations. A previous study in other Korean PD cohorts disclosed a frequency of 3.2%, which is lower than the overall frequency (5-10%).

Method: We recruited 120 patients with idiopathic PD whose age of onset was younger than 55 years (mean age of onset: 48.5±5.3 years) from April 2021 to February 2022. Sanger sequencing of the entire GBA gene were performed. β-glucocerebrosidase (GCase) enzymatic activity in blood samples was measured in patients with GBA mutations.

Results: Among 120 patients with early-onset PD, 12 variants were detected in 15 (12.5%) patients. Ten pathogenic variants [L483P(n=2), N227S(n=2), F252I(n=2), N431S(n=2), R159W(n=1), S310G(n=1), D448H(n=1), P240H(n=1), c.115+1G>A(n=1), and Rec1(L483P, A495P, V499V; n=2)]) were identified. One female patient had compound heterozygous mutations (P240H, N431S). L483P and Rec1 including L483P were common GBA variant (n=4, 28.6%). One novel variant (I442V) predicted to be likely pathogenic was found to have unknown significance (VUS). GCase activity measured in 12 patients with GBA mutations was lower in 11 patients (38.4-79.2%, 54.6±13.4% of controls), except for one with S310G mutation.

Conclusion: GBA mutation was more prevalent than expected in the Korean patients with early-onset subgroup. The mutation spectrum was heterogeneous. Mutations of GBA are also important risk factors for early-onset PD in the Korean population.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-frequency-of-glucocerebrosidase-mutations-in-a-subgroup-of-early-onset-parkinsons-disease-patients-in-the-korean-population/