CLCN6 mutation in an Indian patient with rapidly progressive dementia

The CLC family of chloride channels and transporters plays crucial roles in endosomal/lysosomal function, with dysfunction contributing to protein aggregation and dementia development. CLCN6 mutations are recognized in early-onset neurodegenerative disorders, but reports from India remain limited. We report the first case from India of frontotemporal dementia associated with a novel CLCN6 mutation. A 56-year-old woman presented with rapidly progressive behavioral changes, cognitive decline, and frontotemporal atrophy. Genetic testing revealed a novel heterozygous missense variant c.1615A>G (p.Ser539Gly) in exon 16 of the CLCN6 gene. Comprehensive evaluation excluded autoimmune encephalopathy, and the patient showed partial response to symptomatic treatment. This case expands the geographical and phenotypic spectrum of CLCN6-associated neurodegeneration and highlights the importance of genetic testing in early-onset dementia.