Low-density lipoprotein receptor function and gene mutation in familial hypercholesterolemia

Wu Wenfeng; Sun Liyuan; Wen Wenhui; Wu Yue; Wang Luya

doi:10.3760/j.issn.1673-4777.2018.07.002

Abstract：Objective To analyze the function of low-density lipoprotein receptor (LDL-R) and gene mutation in a patient with homozygous familial hypercholesterolemia(FH) and his relatives.Methods A 12 years old boy with hypercholesterolemia admitted in Beijing Anzhen Hospital,Capital Medical University in August 2016 was enrolled;gene detection showed that he was a homozygous type of FH.The proband and his relatives had blood lipid test and vascular ultrasound;gene mutation was detected and verified by targeted capture chip and the second generation DNA sequencing technology;expression and function of LDL-R in peripheral blood lymphocytes were tested by flow cytometry.Results Levels of serum total cholesterol and low-density lipoprotein cholesterol and thickness of intima-media wall significantly increased in the proband of FH.The exon 8 of LDL-R gene 1 129 base changed from G to T,the encoded protein was cysteine instead of glycine(p.C356G),which was a heterozygous missense mutation.The 9 exon of LDL-R gene 1 268 base changed from T to C,isoleucine was replaced with threonine(p.I402T),which was a heterozygous missense mutation.Expression and binding function of LDL-R significantly decreased (48％ and 40％ of normal person respectively).Conclusions LDL-R gene mutations of the homozygous proband of FH are inherited from mother and father,it may be the molecular basis of the family disease.C356G may be a new mutation type of LDL-R gene in FH patients in China.