Abstract
BACKGROUND: Mutations in the transactive response DNA binding protein (TARDBP) have never been reported in the population of familial frontotemporal dementia (FTD) in Chinese mainland. OBJECTIVE: This study reports for the first time a familial FTD carrying TARDBP mutations in Chinese mainland and summarizes the genetic and clinical features of TARDBP mutant families. METHODS: Case report of comprehensive clinical, genetic and neuroimaging examinations on a 68-year-old male patient diagnosed with behavioral variant FTD (bvFTD). A literature review was also conducted and clinical and genetic features of families with TARDBP mutations were summarized. RESULTS: We reported the bvFTD patient in Chinese with heterozygous mutation of TARDBP. Brain MRI revealed bilateral frontal and temporal atrophy, predominant in the right side. FDG-PET demonstrated frontal and temporal hypometabolism. (18)F-DPA714-PET showed focally elevated bilateral temporal tracer uptake, and (18)F-MNI-1126-PET revealed a reduction in synaptic uptake throughout the brain, especially in the bilateral temporal lobes. In the literature, we found 68 patients from 24 families with 6 different TARDBP mutations in an exon 6. Nine patients presented with symmetrical atrophy involving the frontal, temporal, and parietal lobes, 11 with asymmetrical atrophy, and 5 without atrophy. More than 60.3% of the patients had an onset age earlier than 65 years old and there was a predominance of men. CONCLUSIONS: Our discovery confirmed a pedigree of FTD families and expanded the pedigree mutation spectrum of TARDBP in China. The establishment between phenotype and genotype will aid the diagnosis and treatment of FTD.