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<p><i>NEK1</i> 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 (<i>MAPT</i>,<i> GRN</i>, and <i>C9orf72</i>) was negative. Whole-exome sequencing identified a heterozygous <i>NEK1</i> c.899T &gt; C (p.Ile300Thr) missense variant, currently classified as a variant of uncertain significance. This observation raises the possibility that <i>NEK1</i>-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.</p>

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

  • 期刊论文

  • 发表日期：

    2026年6月23日

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  • Ozlem Totuk,
  • Sevki Sahin

摘要

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.