Genetic Screening in Korean Patients with Frontotemporal Dementia Syndrome

Background: Frontotemporal dementia (FTD) syndrome is a genetically heterogeneous group of diseases. Pathogenic variants in the chromosome 9 open reading frame 72 (C9orf72), microtubule-associated protein tau (MAPT), and progranulin (GRN) genes are mainly associated with genetic FTD in Caucasian populations. Objective: To understand the genetic background of Korean patients with FTD syndrome. Methods: We searched for pathogenic variants of 52 genes related to FTD, amyotrophic lateral sclerosis, familial Alzheimer’s disease, and other dementias, and hexanucleotide repeats of the C9orf72 gene in 72 Korean patients with FTD using whole exome sequencing and the repeat-primed polymerase chain reaction, respectively. Results: One likely pathogenic variant, p.G706R of MAPT, in a patient with behavioral variant FTD (bvFTD) and 13 variants of uncertain significance (VUSs) in nine patients with FTD were identified. Of these VUSs, M232R of the PRNP gene, whose role in pathogenicity is controversial, was also found in two patients with bvFTD. Conclusions: These results indicate that known pathogenic variants of the three main FTD genes (MAPT, GRN, and C9orf72) in Western countries are rare in Korean FTD patients.