Genetics of Frontotemporal Dementia in the Serbian Population: Findings from a Hospital-Based Cohort

Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disorder with autosomal dominant forms most often linked to MAPT, GRN, and C9orf72. We aimed to evaluate the prevalence of pathogenic variants in these genes in a hospital-based cohort of FTD patients assessed at a tertiary referral center in southeastern Serbia.

We studied 58 consecutive patients with FTD spectrum syndromes evaluated at a tertiary referral center. All underwent standardized neurological, neuropsychological, and imaging assessments, and family history was recorded. Genetic testing included validated assays for C9orf72 repeat expansions and next-generation sequencing of MAPT and GRN.

Women comprised 53.45% of the cohort. The mean age was 67.88 years, with mean onset at 61.70 years. Behavioral variant FTD predominated (75.87%), while language forms were less frequent. Positive family history was present in 16 patients (27.59%). Pathogenic variants were identified in three individuals (5.17%): two unrelated carriers of the intronic MAPT mutation c.1920+16C>T and one patient with a C9orf72 expansion. No GRN variants were detected. Mutation frequency was 18.75% in familial cases, while none were found among sporadic patients (p = 0.018). Four of nine relatives were asymptomatic MAPT mutation carriers.

This first genetic study of FTD in southeastern Serbia revealed a lower mutation frequency than in Northern and Western Europe, but similar to cohorts from Southeastern Europe. The detection of MAPT c.1920+16C>T in two unrelated families extends the geographic range of this splice-site variant and underscores the importance of systematic genetic testing and larger collaborative studies in the Balkans.