Mutation detection in Chinese patients with familial hypercholesterolemia.

Hao Huang,Min-Jie Lin,Kun Xia,Jing-Jing Li,Zhi-Jian He,Shui-Ping Zhao,Rong Xiang,Liang-Liang Fan,Ran Du,Ya-Qin Chen

doi:10.1186/s40064-016-3763-3

Abstract

BackgroundFamilial hypercholesterolemia (FH) is the first molecularly and clinically characterized genetic disease of lipid metabolism. It is an autosomal dominant disorder with significantly elevated levels of total cholesterol and low density of lipoprotein cholesterol in serum, which would lead to extensive xanthomas and premature coronary heart disease. Mutations in low density lipoprotein receptor (LDLR), proprotein convertase subtilisin/kexin type 9 and Apo lipoprotein B-100 (APOB) have been identified to be the underlying cause of this disease.MethodsGenetic testing and reports of the mutations in the Chinese population are still limited. In this study, 11 unrelated Chinese FH families were enrolled to detect the candidate gene variants by DNA direct sequencing.Results and conclusionWe identified 12 mutations (11 in LDLR and one in APOB) in ten FH families. Three novel LDLR mutations (c.516C>A/p.D172E, c.1720C>A/p.R574S and c.760C>T/p.Q254X) were identified and co-segregated with the affected individuals in the families. Our discoveries not only further supports the significant role of LDLR in FH, but also expands the spectrum of LDLR mutations. These new insights will contribute to the genetic diagnosis and counseling of FH patients.

Highlights

Familial hypercholesterolemia (FH) is the first molecularly and clinically characterized genetic disease of lipid metabolism
Association for Cardiovascular Prevention & Rehabilitation et al 2011; Goldberg et al 2011; Hovingh et al 2013). Such high plasma TC and LDL-C levels may result in xanthelasmas and atherosclerotic plaques, the primary factors causing premature coronary heart disease (CHD) (Najam and Ray 2015)
Together with the p.R3527 mutation of Apo lipoprotein B-100 (APOB) (NM_000384) were performed with polymerase chain reaction (PCR; primer sequences will be provided upon requests)

Summary

Introduction

Familial hypercholesterolemia (FH) is the first molecularly and clinically characterized genetic disease of lipid metabolism It is an autosomal dominant disorder with significantly elevated levels of total cholesterol and low density of lipoprotein cholesterol in serum, which would lead to extensive xanthomas and premature coronary heart disease. Familial hypercholesterolemia (FH, OMIM#143890) is one of the most severe lipid dysfunctions, characterized by elevated total cholesterol and low density of lipoprotein cholesterol amounts in serum (Jannes et al 2015) It is inherited in an autosomal dominant fashion, with frequencies of heterozygotes and homozygotes estimated at 1:200 and 1:300,000 worldwide (Foody and Vishwanath 2016). Association for Cardiovascular Prevention & Rehabilitation et al 2011; Goldberg et al 2011; Hovingh et al 2013) Such high plasma TC and LDL-C levels may result in xanthelasmas and atherosclerotic plaques, the primary factors causing premature coronary heart disease (CHD) (Najam and Ray 2015). The levels of TC and LDL-C can be effectively reduced by statin (Vogt 2015)

Methods

Results

Conclusion