Genetic Spectrum and Clinical Heterogeneity of Chinese Frontotemporal Dementia Patients: Data from PUMCH Dementia Cohort.

BACKGROUND

There are relatively few data on the genetic spectrum of Chinese frontotemporal dementia (FTD) population.

OBJECTIVE

With the dementia cohort of Peking Union Medical College Hospital, we aim to illustrate the genetic spectrum of FTD patients, as well as the phenotypic heterogeneity of FTD-gene variant carriers.

METHODS

204 unrelated, clinically diagnosed FTD patients of Chinese ancestry were enrolled. All the participants received demographic survey, history inquiry, physical examination, cognitive assessment, blood biochemical test, brain CT/MRI, and gene sequencing.

RESULTS

56.4% (115/204) participants were clinically diagnosed with behavioral variant of FTD, 20.6% (42/204) with nonfluent/agrammatic variant primary progressive aphasia (PPA), 20.1% (41/204) with semantic variant PPA, and 2.9% (6/204) with mixed variant PPA. 11.8% (24/204) subjects harbored the potential causative variants in FTD-related genes, including the MAPT (n = 7), TBK1 (n = 7), GRN (n = 2), TBK1+GRN (n = 1), VCP (n = 1), TARDBP (n = 1), UBQLN2 (n = 1), SQSTM1 (n = 1), DCTN1 (n = 1), HNRNPA1 (n = 1), and C9orf72 GGGGCC repeats (n = 1). The TBK1 T31fs, T457fs, K622fs, c.359-1G>A, the VCP P188T, and the GRN P50fs, P439fs were novel pathogenic/likely pathogenic variants. The TBK1 carriers showed a later disease onset and a higher incidence of parietal atrophy relative to the MAPTcarriers.

CONCLUSION

There is genetic and clinical heterogeneity among Chinese FTD population. The TBK1 has a high mutation frequency in Chinese FTD patients.