TARDBP gene mutation in a Chinese family with frontotemporal dementia: A case report and literature review

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.