Objective: We aimed to investigate the genetic spectrum of corticobasal syndrome (CBS) in a sizable Asian cohort.

Background: CBS is a rare, rapidly progressive neurodegenerative disorder characterized by asymmetric motor and cortical dysfunction. The disease generally carries a poor prognosis with limited therapeutic options. Although CBS is primarily considered a sporadic disorder, a subset of patients harbor pathogenic genetic variants. Additionally, genome-wide association studies (GWAS) of its underlying pathology, corticobasal degeneration (CBD), have identified several risk loci in cohorts of European ancestry. However, the genetic landscape remains critically under-characterized in Asian populations.

Method: We analyzed whole exome sequencing data from a multicenter Asian cohort of 99 clinically diagnosed CBS patients (Taiwan, n=61; Japan, n=23; Malaysia, n=15). To ensure clinical relevance, variant curation was restricted to rare alleles (minor allele frequency < 0.01) within genes structurally or functionally linked to CBS-related phenotypes and neurodegenerative pathogenesis.

Results: Among the 99 patients (mean age of onset 67.80 ± 8.83 years; 38.3% male), 12 had a family history of parkinsonism, dementia, or related neurodegenerative disorders. Within this familial subset, 2 patients carried heterozygous pathogenic or likely pathogenic (P/LP) variants and 3 harbored rare variants of uncertain significance (VUS). In total, 9 patients (9.09%; Taiwan, n=8; Malaysia, n=1) carried 10 P/LP variants. Notably, one patient carried two heterozygous variants in POLG located in cis, while the remaining eight patients each harbored a single heterozygous variant. Among all identified P/LP variants, one was novel (GRN c.20G>A:p.W7*). In addition, 31 heterozygous rare VUS were identified in 25 patients (25.3%; Taiwan, n=11; Japan, n=12; Malaysia, n=2). The P/LP variants were in genes including MAPT (n=3), GRN (n=1), TBK1 (n=1), ABCA7 (n=2), POLG (n=2), and PRNP (n=1). Furthermore, the 31 heterozygous rare VUS spanned genes including ABCA7 (n=5), MAPT (n=3), BSN (n=3), APP (n=2), PSEN1 (n=1), LRRK2 (n=4), LRP10 (n=2), TMEM175 (n=2), and single cases in GFAP, GRN, MOBP, NEFM, SLCO1A2, SQSTM1, TENM4, CCNF, and ZNF512B.

Conclusion: Our study reveals a highly complex genetic architecture of CBS in Asian populations, distinct from those reported in populations of European descent.

References: 1. Kouri N, Ross OA, Dombroski B, et al. Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy. Nat Commun. 2015;6:7247. Published 2015 Jun 16. doi:10.1038/ncomms8247

« Back to 2026 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/exploring-the-genetic-landscape-of-corticobasal-syndrome-in-asian-populations/