Kemunculan teknologi penyuntingan genom, terutamanya CRISPR/Cas9, telah mengubah dan merevolusikan landskap bidang genetik dan biologi molekul dengan begitu drastik. Sistem CRISPR/Cas9 diadaptasi daripada sistem adaptasi imuniti bakteria, menggunakan enzim Cas9 yang dipandu oleh sgRNA untuk penyingkiran gen atau penyuntingan genom secara jitu. Walau bagaimanapun, cabaran seperti kesan luar sasaran (off-target effects) telah mendorong pembangunan beberapa varian Cas9 seperti dCas9. dCas9 diubah suai untuk tidak memiliki sebarang aktiviti endonuklease dan kini dCas9 telah digunakan untuk pelbagai aplikasi yang melangkaui fungsi tradisional CRISPR/Cas9 sebagai kaedah pengeditan genom. Selain itu, teknologi terkini penyuntingan perdana (prime editing) telah menggabungkan enzim Cas9 yang diubahsuai bersama enzim transkriptase berbalik (reverse transcriptase) untuk meningkatkan lagi tahap keberkesanan penyuntingan genom secara jitu. Walaupun wujud kerisauan terhadap pertimbangan etika dan kebimbangan terkait keselamatan, namun teknologi ini menjanjikan dampak yang besar di dalam menangani penyakit genetik serta aplikasi dalam bidang perubatan jitu (precision medicine). Memahami dan mengoptimumkan potensi CRISPR/Cas9 dan teknologi penyuntingan perdana menandakan bermula era baharu dalam bidang penyelidikan berkaitan biologi dan perubatan, dan seterusnya menyediakan satu platform untuk penyuntingan genom yang tepat dan pengawalseliaan proses transkripsi gen.

Background: Mutations in glucocerebrosidase (GBA) have been associated with the risk of developing Parkinson’s disease (PD) in different ethnic populations. The prevalence of GBA mutations among Malay PD patients is unknown. Thus, the aim of this study was to determine the frequency of GBA mutations among Malay PD patients, focusing on early (EOPD) and late-onset (LOPD) patients. Methods:EOPD (n = 50) and LOPD (n = 50) patients along with 50 ethnically and age-matched control wererecruited. The GBA exons of these patients were sequenced using the Ion Torrent PGMTM System. Results: Five heterozygous mutations exclusive to EOPD patients were identified; c.-203A>G,p.S146L, p.R159Q, p.L483P and p.L483R+c.-145G>A. In LOPD patients, c.543C>T(p.(F181=)), c.28-10C>A and p.R202Q were identified in which this p.R202Q was also present in a control subject. In addition, c.259C>A(p.(R87=)) and c.-145G>A were identified in two control subjects. In summary, we observed GBA mutations in 8% and 6% of Malay PD cases and control subject, respectively. The prevalence of GBA mutations was higher in EOPD (10%) than LOPD (6%). However, these differences were not statistically significant; [PD vs. controls: OR = 1.36, 95%CI 0.35-5.38, p = 0.752] and [EOPD vs. LOPD: OR = 1.74, 95%CI 0.39-7.71, p = 0.715]. Conclusion: We identified five exclusive heterozygous GBA mutations in EOPD patients which might predict the increase susceptibility of Malays to develop PD at young age. These findings could add knowledge into the existing evidences linking genetic alterations in GBA and PD.