LAUSR

BACKGROUND We previously showed that patients without pathogenic variants in the LDLR and PCSK9 genes comprised approximately 40% of familial hypercholesterolemia (FH) cases. OBJECTIVE Our aim was to identify novel causative variants in Japanese patients with FH. METHODS Whole-exome sequencing was performed in 216 family members from 123 families without pathogenic variants in the LDLR and PCSK9 genes. Clinical and biochemical data were gathered from the family members. RESULTS The known p.(Arg3527Gln) variant in the APOB gene was identified in one Japanese family. The other pathogenic variants in the APOB gene were not identified. The p.(Arg3527Gln) variant was not identified in the other 113 index cases without pathogenic variants in the LDLR and PCSK9 genes. The allele frequency of the p.(Arg3527Gln) variant was 0.0001 in the general Japanese population. CONCLUSION This is the first report of Japanese cases of FH caused by a known pathogenic APOB variant, p.(Arg3527Gln).