Behavioral variant frontotemporal dementia associated with a NEK1 missense variant: exploring a possible phenotypic association.

NEK1 variants are recognized genetic contributors to amyotrophic lateral sclerosis (ALS) and have occasionally been reported within the ALS-frontotemporal dementia (FTD) spectrum. However, their association with isolated behavioral variant frontotemporal dementia (bvFTD) remains unclear. Here, we describe a 69-year-old man who developed progressive behavioral symptoms beginning in his early 60s. Cognitive evaluation demonstrated reduced verbal fluency with relative preservation of memory functions. Structural and functional neuroimaging demonstrated right-predominant frontotemporal atrophy and hypometabolism. Genetic testing for common FTD-associated genes (MAPT, GRN, and C9orf72) was negative. Whole-exome sequencing identified a heterozygous NEK1 c.899T > C (p.Ile300Thr) missense variant, currently classified as a variant of uncertain significance. This observation raises the possibility that NEK1-associated disease may extend beyond ALS or ALS-FTD phenotypes and may include isolated bvFTD presentations. However, further genetic and functional studies are required to clarify the clinical significance of this variant.