Objective: We investigated the mutation spectrum of glucocerebrosidase (GBA) gene in Korean patients with Parkinson’s disease (GBA-PD).

Background: Mutations in the GBA gene represent important genetic risk factors for PD. The pathogenicity of different variants varies largely. To date, over 100 different GBA mutations have been reported, with ethnic differences in the mutational spectrum. However, there are few studies on the mutation spectrum of GBA-PD in Koreans.

Method: Fifty Korean patients with GBA-PD were enrolled in this study. We identified 25 PD patients by sequencing the entire GBA gene. In addition, 25 PD patients were recruited through review of two previously reported literatures. The pathogenicity of GBA mutations is classified as ‘severe’ or ‘mild’ based on the established risks reported for PD.

Results: Seventeen different mutations were detected. Eleven mutations (p.L483P [n = 9, previously known as L444P], p.R296Q [n = 8, R257Q], p.N227S [n = 4, N188S], p.F252I [n = 4, F213I], p.R159W [n = 3, R120W], c.115+1G>A [n = 3, IVS2 + 1], p.D448H [n = 2, D409H], p.V230G [n = 2, V191G], p.P240H [n = 2, P201H], Rec1; p.L483P, p.A495P, p.V499V [n = 2, RecNciI; L444P+A456P+V460V], p.R202* [n = 1, R163X],) are known to be associated with Gaucher’s disease (GD) and PD and are classified as severe mutations for developing PD. p.S310G [n = 4, S271G] and p.N409S [n = 1, N370S] are classified as mild variants. p.N431S [n = 2, N392S], has already been reported in PD, but the significance of PD remains unknown. p.G85E [n = 2, G46E], p.P221L [n = 1, P182L] have been reported in GD, but not reported in PD. One patient had compound heterozygous mutations (p.P240H, p.N431S). One novel variant (p.I442V) that is likely pathogenic was found to have unknown significance based on the American College of Medical Genetics and Genomics guidelines. p.E365K (E326K) and p.T408M (T369M) were absent.

Conclusion: Various GBA mutations were identified in the Korean GBA-PD patients. p.L483P and p.R296Q were the two most common mutations. Some risk variants common in the western countries were rare in the Korean population.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-spectrum-of-gba-mutations-in-the-korean-population-with-parkinsons-disease/