Phenotypic diversity of frontotemporal lobar degeneration in two novel GRN variants from Colombia

INTRODUCTION Pathogenic progranulin ( GRN) variants are among the main genetic causes of frontotemporal lobar degeneration (FTLD). These variants have been predominantly reported in European cohorts, but their characterization in Latin America remains scarce. We describe two Colombian cases with novel GRN variants with amnestic and semantic syndromes leading to an initial diagnosis of Alzheimer's disease (AD). METHODS We conducted clinical, neuropsychological, neuroimaging, and genetic analysis. Biomarkers were included for one case. RESULTS At 42 years old, Case 1 presented a predominant amnestic profile and carried the GRN c.21 G > A (p.Trp7*) variant. Case 2 debuted with a semantic impairment at 62 years old and was a carrier of GRN c.1098T > A (p.Cys366*) variant. Brain imaging revealed asymmetric temporal atrophy, and biomarkers supported diagnosis of FTLD. DISCUSSION GRN variants can mimic early‐onset AD. An integrative approach including serial clinical, genetic, brain imaging, and biomarker analysis are essential for diagnosing Amnestic variants of FTLD in admixed genetic populations.