Expanding the genetic spectrum of corticobasal syndrome: novel CCNF p.M394L variant from a South Asian cohort.

Abstract

Corticobasal syndrome (CBS) is a rare neurodegenerative disorder characterized by asymmetric motor symptoms, cognitive impairment, and cortical dysfunction. While CCNF gene mutations have been reported in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), their role in CBS spectrum remains unexplored. This study aimed to investigate a 48-year-old patient of South Asian origin, presenting with progressive cognitive decline, behavioral disturbances, and asymmetric motor symptoms characteristic of overlap CBS syndrome. Detailed cognitive and behavioral assessments were conducted, along with brain imaging and whole-exome sequencing. Structural modeling was performed to assess the functional impact of the novel CCNF variant. The family history indicated an autosomal dominant inheritance pattern of progressive cognitive decline, further suggesting genetic predisposition. Brain imaging revealed asymmetric atrophy and hypometabolism in the left temporoparietal and prefrontal regions. Genetic analysis identified a novel heterozygous missense variant (p.Met394Leu) in the CCNF gene. Structural modeling and in-silico prediction tools suggested deleterious effects, though its functional significance remains uncertain. The study reports a potential link between CCNF variants and CBS in a South Asian family, expanding the genetic spectrum of overlap CBS. While the findings suggest potential pathogenicity, further research is required to confirm this association and elucidate the underlying mechanisms.