Semantic variant primary progressive aphasia with ANXA11 p.D40G

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• Pathogenic variants in annexin A11 (ANXA11) are linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
• The role of ANXA11 variations in FTD, particularly in the Korean population, requires further investigation.

Purpose of the Study:

• To explore the prevalence and significance of ANXA11 pathogenic variants in a Korean FTD cohort.
• To investigate the potential genetic contribution of ANXA11 variation to FTD development.

Main Methods:

• Utilized next-generation sequencing (NGS) to screen for ANXA11 pathogenic variants.
• Analyzed two nationwide FTD cohorts in Korea.

Main Results:

• Identified the pathogenic ANXA11 variant c.119A>G (p.D40G) in six patients with semantic variant primary progressive aphasia (svPPA).
• This variant represented 5.5% of the svPPA cohort and 2.3% of the overall FTD cohort.
• One patient with the variant later developed symptoms suggestive of ALS.

Conclusions:

• The ANXA11 p.D40G variant is linked to a sporadic FTD syndrome, specifically svPPA.
• This variant may promote the co-fibrillization of ANXA11 and TAR DNA-binding protein-43 (TDP-43), contributing to frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) type C.
• ANXA11 (p.D40G) represents a potential genetic cause for svPPA and FTLD-TDP type C.