Familial Hypercholesterolemia with Two Mutations in LDLR Gene: A Case Report and Literature Review

Hui Zhou,Thachapol Napawan,Xiaoxiao Song,Linjin Wu,Bo Sun,Wei Gu

doi:10.4236/ijcm.2017.810052

Abstract

We report a case of Familial hypercholesterolemia (FH) with two mutations in low density lipoprotein receptor (LDLR) gene and speculate the correlation between the newly discovered mutation type of LDLR gene and FH. We collected and analyzed the clinical data of the proband in the case and her immediate family members, and detected the LDLR, Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK-9) and Apolipoprotein B (Apo B) gene in the peripheral blood of all the participants. We found that the curative effect of the patient is limited, but no obvious complication was detected. Genetic testing results pointed out that there were two mutations in the patient’s LDLR gene. One was p.W483* mutation in exon 10 (c. 1448 G > A), another was p.T534I mutation in exon 11 (c. 1601 C > T). The p. W483* mutation in exon 10 was detected in the father and sister, additionally p. T534I mutation in exon 11 was detected in the mother. Both the two LDLR gene mutations are inherited from her parents. We hypothesize that the patient in this case was a complex heterozygote. The newly discovered mutation gene (T534I) may be one of the important causes of dyslipidemia in patients, and its adverse effects are more serious than W483* which have been reported. Also, we predict that the T534I mutation will not cause serious early onset of cardiovascular complications.

Highlights

We report a case of Familial hypercholesterolemia (FH) with two mutations in low density lipoprotein receptor (LDLR) gene and speculate the correlation between the newly discovered mutation type of LDLR gene and FH
Gene mutations in the gene encoding are the major causes of FH, such as LDLR, Apolipoprotein B (Apo B), the Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK-9), and LDLR gene mutations are the most common [2]. 50% of the FH patients have been confirmed with one or more mutations of LDLR gene [12], so gene detecting of LDLR is of great significance for the further research of the molecular basis of the pathogenesis of FH
The effect of p.T534I mutation on the synthesis and function of LDLR is not clear, further experiments are needed to prove the correlation between the mutant gene and the pathogenesis of FH

Summary

Introduction

FH can be divided into two clinical manifestations: the relatively milder heterozygous form and more severe homozygous form [2]. It can usually be diagnosed definitely according to clinical features such as family history, blood lipid index, genetic testing and so on. The plasma low-density lipoprotein cholesterol (LDL-c) levels are higher, and body multiple xanthomas are more common. Some of the homozygous patients are more likely to an early onset and of cardiovascular diseases. FH is the main risk factor of premature atherosclerosis, coronary artery stenosis and other cardiovascular disease, early recognition and intervention can reduce the morbidity and mortality of cardiovascular events effectively [7] [8]

Case Report

Screening for Cardiovascular Complications

Genealogical Analysis

Findings

Discussion and Literature

Conclusion