Analysis of clinical phenotypes and variants of LDLR gene in two Chinese patients with familial hypercholesterolemia.
10.3760/cma.j.cn511374-20211122-00929
- Author:
Kexin WANG
1
;
Tao SUN
;
Xiaoping ZHANG
;
Yahui ZHANG
;
Hai GAO
;
Yanlong REN
;
Xiaoyan LI
Author Information
1. Coronary Heart Disease Center, Department of Internal Medicine-Cardiovascular, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing 100029, China. xiaoyanli82@163.com.
- Publication Type:Journal Article
- MeSH:
Humans;
China;
Hyperlipoproteinemia Type II/genetics*;
Phenotype;
Receptors, LDL/genetics*
- From:
Chinese Journal of Medical Genetics
2022;39(12):1344-1348
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the correlation between clinical phenotypes and pathogenic variants in two patients with familial hypercholesterolemia.
METHODS:Both patients were subjected to whole exome sequencing (WES) with a focus on the analysis of genes associated with dyslipidemia. Candidate variants were verified by Sanger sequencing of the patients and their family members.
RESULTS:WES revealed that the proband 1 has harbored two heterozygous variants of the LDLR gene, namely c.1360G>A (p.D454N) and c.292G>A (p.G98S), whilst proband 2 has harbored a heterozygous c.321T>G (p.C107W) variant of the LDLR gene. Based on the guidelines from the American College of Medical Genetic and Genomics (ACMG), the above variants were respectively predicted to be likely pathogenic (PM1+PM2+PP2+PP3+PP4+PP5), variant of unknown significance (PM1+PP2+PP3), and likely pathogenic (PM1+PM2+PP2+PP4+PP5). Treatment with PCSK9 inhibitor has attained a significant effect in proband 1 but no apparent effect in proband 2.
CONCLUSION:Variants of the LDLR gene probably underlay the familial hypercholesterolemia in the two pedigrees. The difference in the severity of the clinical phenotypes and response to PCSK9 inhibitor treatment between the two probands may be attributed to the different genotypes of the LDLR gene. Genetic testing not only can provide a basis for clinical diagnosis, but also facilitate the choice of lipid-lowering drugs.
