{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T08:23:28Z","timestamp":1793694208974,"version":"4.5.1"},"reference-count":43,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2025,11]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Early\u2010onset Parkinson's disease (EOPD) affects approximately 10% to 20% of PD patients, with\n PRKN<\/jats:italic>\n mutations being the commonest cause. Genetic studies on EOPD in Southeast Asians, especially indigenous populations, are limited.\n <\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n \n To investigate the frequency and clinical phenotypes of EOPD and\n PRKN<\/jats:italic>\n mutations in indigenous populations from Sabah state, Malaysia, and to further characterize the high\u2010frequency\n PRKN<\/jats:italic>\n exon 3 deletion in this cohort via breakpoint mapping.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We recruited 284 indigenous Sabahans (184 PD patients, comprising 157 probands and 100 controls). Patients were clinically phenotyped, and\n PRKN<\/jats:italic>\n mutational screening and breakpoint mapping performed using multiplex ligation\u2010dependent probe amplification, polymerase chain reaction, and Sanger sequencing.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Notably, 43.9% (n\u2009=\u200969\/157) of probands had EOPD. Among them, 56.5% (n\u2009=\u200939\/69) carried biallelic\n PRKN<\/jats:italic>\n mutations, with homozygous exon 3 deletion accounting for two\u2010thirds of the mutations. Remarkably, all\n PRKN<\/jats:italic>\n \u2010PD patients carried at least one exon 3 deletion. Patients of the Dusun tribe had the highest frequency of biallelic\n PRKN<\/jats:italic>\n mutations (61.8%). Two unique\n PRKN<\/jats:italic>\n exon 3 deletion breakpoints were identified in all carriers, suggesting a possible founder effect. Among\n PRKN<\/jats:italic>\n \u2010PD patients, those with homozygous exon 3 deletions had a non\u2010significant earlier age of onset (35.8\u2009\u00b1\u200910.2 vs. 40.1\u2009\u00b1\u20099.9) and worse disability after controlling for age and disease duration.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n We found a strikingly high prevalence of EOPD and\n PRKN<\/jats:italic>\n mutations in indigenous Sabahans, contributing novel data to the very scarce PD genetics literature on global indigenous populations, and highlighting the discovery of populations at high risk of EOPD possibly due to a combination of founder effect and consanguinity. \u00a9 2025 International Parkinson and Movement Disorder Society.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mds.70015","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T08:50:48Z","timestamp":1757926248000},"page":"2407-2418","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Very High Frequency of Early\u2010Onset Parkinson's Disease and\n \n PRKN<\/i>\n <\/scp>\n Mutations among Indigenous Patients in Sabah, Malaysia"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9319-0768","authenticated-orcid":false,"given":"Yi Wen","family":"Tay","sequence":"first","affiliation":[{"name":"Department of Biomedical Science, Faculty of Medicine Universiti Malaya Kuala Lumpur Malaysia"},{"name":"Division of Neurology, Department of Medicine, Faculty of Medicine Universiti Malaya Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6235-3712","authenticated-orcid":false,"given":"Joshua Chin Ern","family":"Ooi","sequence":"additional","affiliation":[{"name":"Department of Neurology Queen Elizabeth Hospital Kota Kinabalu Sabah Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shen\u2010Yang","family":"Lim","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Medicine, Faculty of Medicine Universiti Malaya Kuala Lumpur Malaysia"},{"name":"The Mah Pooi Soo and Tan Chin Nam Centre for Parkinson's and Related Disorders, Faculty of Medicine Universiti Malaya Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuen Kang","family":"Chia","sequence":"additional","affiliation":[{"name":"Department of Neurology Queen Elizabeth Hospital Kota Kinabalu Sabah 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