• Yu Han, Lin Zhang, Huimin Tao, Jiebin Wu, and Jingfang Zhai.
• Affiliated Xuzhou Clinical College of Xuzhou Medical University, Xuzhou, China.
• Medicine (Baltimore). 2023 Aug 11; 102 (32): e34534e34534.

RationaleFamilial hypercholesterolemia (FH) is an autosomal dominant genetic disorder typically caused by low density lipoprotein receptor (LDLR) gene mutation. Herein, we reported a FH pedigree with polygenic variants: LDLR, apolipoprotein B (APOB), and epoxide hydrolase 2 (EPHX2).Patient ConcernsA 10-year-old boy mainly presented multiple skin xanthomas and hypercholesterolemia. His family visited our hospital and was performed with pedigree whole exome sequencing (WES) at 20 + 3 weeks gestation of the mother's second pregnancy.DiagnosesBased on the clinical features and genetic analysis, the pedigree was diagnosed with familial hypercholesterolemia.InterventionsAfter genetic counseling, the couple opted to continue the pregnancy. Treatment advice and follow-up were offered to them.OutcomesA novel compound heterozygous LDLR mutation: c.1009G>T and c.68-2A>G, derived from his parents respectively was revealed through pedigree WES, meanwhile, a maternal APOB gene variant: c.1670A>G and a paternal EPHX2 gene variant: c.548 dup of the proband were found together. Furthermore, the same compound heterozygous LDLR mutation as his was confirmed in his sister without APOB and EPHX2 variants in her fetal stage.LessonsWES combined with clinical features is essential for the diagnosis of FH, however, prenatal genetic testing results might bring more challenges to prenatal genetic counseling. Furthermore, it is more important to provide the guidance and early intervention for such families in the long run.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.

13 keywords...

hide…