A novel GRN mutation presenting with an amnestic phenotype mimicking early onset Alzheimer disease, a case report

Abstract

Frontotemporal dementia is a neurodegenerative disease with a variety of clinical presentations. Despite the idiopathic form is the most frequent, it may be often associated with heritable mutations, sometimes characterized by unusual clinical manifestations. Herein we present a case report of a 56-year-old man who developed an unusual onset of disease, which was marked by an episodic memory impairment, spatial disorientation, and apathy. The patient’s age and his atypical clinical presentation raised the suspicion of a genetic substrate. Genetic investigation revealed a new mutation of the GRN gene, possibly pathogenic, that had never been described before. Pathogenicity was confirmed by plasma progranulin assay, which was below normal range. Our case underscores the clinical heterogeneity of GRN mutations, which can manifest in different phenotype ranging from frontotemporal dementia to Alzheimer Disease-Like phenotype. These findings highlight the importance of GRN genetic screening in patients presenting with atypical phenotype, as identifying these variants remains essential to clarify the full spectrum of gene’s functional impact and ensuring accurate diagnostic stratification.