Novel compound heterozygous mutations in low density lipoprotein receptor gene causes a severe phenotype in a Chinese hypercholesterolemia family

Cheng,Xinyao; Huang,Yifang; Qiu,Xueping; Cheng,Xiaohuan; Jin,Yalei; Hu,Yafei; Yang,Bing; Zhao,Jingbo; Lei,Yuhua; Zheng,Fang

doi:10.3892/etm.2018.6205

Novel compound heterozygous mutations in low density lipoprotein receptor gene causes a severe phenotype in a Chinese hypercholesterolemia family

Authors:
- Xinyao Cheng
- Yifang Huang
- Xueping Qiu
- Xiaohuan Cheng
- Yalei Jin
- Yafei Hu
- Bing Yang
- Jingbo Zhao
- Yuhua Lei
- Fang Zheng
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Affiliations: Cardiovascular Division, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, P.R. China, Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, P.R. China, Geriatrics Division, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, P.R. China, Ultrasonography Division, Enshi Center Hospital, Enshi, Hubei 445000, P.R. China
Published online on: May 23, 2018 https://doi.org/10.3892/etm.2018.6205
Pages: 901-907

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Abstract

Mutations in the low density lipoprotein receptor (LDLR) gene serve a causative role in the pathophysiology of familial hypercholesterolemia (FH), a common autosomal inherited disorder characterized by abnormal lipid metabolism. The aim of the present study was to investigate genetic defects in a Chinese family with FH. Clinical features and family histories were collected, as were the results of various laboratory tests, including determinations of serum lipid concentrations, ultrasonography and angiography results. Potential mutations in LDLR were screened using direct polymerase chain reaction (PCR) sequencing. Multiple sequence alignments, structure and hydrophobicity predictions were performed in silico. Novel compound heterozygote mutations in LDLR of the proband were identified, with a Trp577Term‑bearing maternal allele and a Pro685Leu‑bearing paternal allele. The proband, a 27‑year‑old male, had severe and diffuse coronary stenosis and non‑ST segment elevation myocardial infarction, as well as multiple skin xanthomas and high serum lipid levels. The allele‑dosage‑dependent clinical features, including hypercholesterolemia and peripheral arterial atherosclerosis, were observed in the proband and the other heterozygous patients. Therefore, the coexistence of Pro685Leu and Trp577Term mutations in LDLR is a novel compound heterozygosis in Chinese patients and may lead to a severe FH phenotype. The explanation for the existence of compound heterozygous mutations instead of homozygous mutations in this particular family requires further study.

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