Analysis of frontotemporal dementia, amyotrophic lateral sclerosis, and other dementia-related genes in 107 Korean patients with frontotemporal dementia

摘要

To identify pathogenic variants in 107 Korean patients with sporadic frontotemporal dementia (FTD), 46 genes related to FTD, amyotrophic lateral sclerosis, and other dementias were screened by next-generation sequencing. Hexanucleotide repeats inC9orf72gene were also tested by repeat-primed polymerase chain reaction. Next-generation sequencing revealed one known pathogenic variant (c.708+1G>A) in theGRNgene in a patient with behavioral variant FTD (bvFTD). In addition, a novel in-frame deletion (c.2675_2683del) in theCSF1Rgene was identified in a patient with bvFTD who had severe bifrontal atrophy with frontal subcortical white matter changes. Novel compound heterozygous variants in theAARS2gene, c.1040+1G>A and c.636G>A (p.Met212Ile), were found in a patient with bvFTD. Forty-six variants of uncertain significance were detected in other patients. None of the patients had expanded hexanucleotide repeats inC9orf72. These results show that pathogenic variants of known FTD genes are rare in Korean FTD patients but theCSF1RandAARS2genes should be screened for a genetic diagnosis of FTD or other dementias.