Department of Molecular Innovation in Lipidology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.
Department of Genomic Medicine, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.
J Clin Lipidol. 2020 Jul-Aug;14(4):482-486. doi: 10.1016/j.jacl.2020.05.007. Epub 2020 May 22.
We previously showed that patients without pathogenic variants in the LDLR and PCSK9 genes comprised approximately 40% of familial hypercholesterolemia (FH) cases.
Our aim was to identify novel causative variants in Japanese patients with FH.
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.
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.
This is the first report of Japanese cases of FH caused by a known pathogenic APOB variant, p.(Arg3527Gln).
我们之前发现 LDLR 和 PCSK9 基因中无致病性变异的患者约占家族性高胆固醇血症（FH）病例的 40%。
我们旨在鉴定日本 FH 患者中的新型致病变异。
对 123 个 LDLR 和 PCSK9 基因无致病性变异的家族的 216 名家族成员进行全外显子组测序。从家族成员中收集临床和生化数据。
在一个日本家族中发现了 APOB 基因中的已知 p.(Arg3527Gln)变异。未鉴定出 APOB 基因中的其他致病性变异。在其他 113 名 LDLR 和 PCSK9 基因无致病性变异的索引病例中也未鉴定出 p.(Arg3527Gln)变异。该 p.(Arg3527Gln)变异在一般日本人群中的等位基因频率为 0.0001。
这是首例由已知致病性 APOB 变异 p.(Arg3527Gln)引起的日本 FH 病例报告。
