Glucocerebrosidase (GBA) gene variants in a multi-ethnic Asian cohort with Parkinson's disease: mutational spectrum and clinical features

Lim JL 1 , Lohmann K 2 , Tan AH 3 , Tay YW 1 , Ibrahim KA 4 , Abdul Aziz Z 4 Show all authors , Mawardi AS 5 , Puvanarajah SD 5 , Lim TT 6 , Looi I 7 , Ooi JCE 8 , Chia YK 8 , Muthusamy KA 9 , Bauer P 10 , Rolfs A 10 , Klein C 2 , Ahmad-Annuar A 11 , Lim SY 12

Affiliations 

  • 1 Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • 2 Institute of Neurogenetics, University of Luebeck, Luebeck, Germany
  • 3 The Mah Pooi Soo and Tan Chin Nam Centre for Parkinson's and Related Disorders, University of Malaya, Kuala Lumpur, Malaysia
  • 4 Department of Medicine, Hospital Sultanah Nur Zahirah, Kuala Terengganu, Malaysia
  • 5 Department of Neurology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia
  • 6 Island Hospital, Penang, Malaysia
  • 7 Department of Medicine and Clinical Research Centre, Hospital Seberang Jaya, Penang, Malaysia
  • 8 Department of Neurology, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia
  • 9 Division of Neurosurgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • 10 Centogene AG, Am Strande 7, 18057, Rostock, Germany
  • 11 Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. azlina_aa@um.edu.my
  • 12 The Mah Pooi Soo and Tan Chin Nam Centre for Parkinson's and Related Disorders, University of Malaya, Kuala Lumpur, Malaysia. limshenyang@gmail.com
J Neural Transm (Vienna), 2022 Jan;129(1):37-48.
PMID: 34779914 DOI: 10.1007/s00702-021-02421-0

Abstract

GBA variants are associated with increased risk and earlier onset of Parkinson's disease (PD), and more rapid disease progression especially with "severe" variants typified by p.L483P. GBA mutation screening studies from South-East Asia, with > 650 million inhabitants of diverse ancestries, are very limited. We investigated the spectrum of GBA variants, and associated clinico-demographic features, in a multi-ethnic PD cohort in Malaysia. Patients (n = 496) were recruited from seven centres, primarily of Chinese (45%), Malay (37%), and Indian (13%) ethnicities. All GBA coding exons were screened using a next-generation sequencing-based PD gene panel and verified with Sanger sequencing. We identified 14 heterozygous GBA alleles consisting of altogether 17 missense variants (8 classified as pathogenic or likely pathogenic for PD) in 25 (5.0%) patients, with a substantially higher yield among early (

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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