Abstract
Familial hypercholesterolaemia (FH) is an autosomal dominant genetic disorder, associated with elevated level of serum low-density lipoprotein-cholesterol (LDL-C), which can lead to premature cardiovascular disease (CVD). Mutations in low density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) have been identified to be the underlying cause of this disease. Genetic research of FH has already been extensively studied all over the world. However, reports of FH mutations in the Chinese population are still limited. In this paper, 20 unrelated FH families were enrolled to detect the candidate gene variants in Chinese FH population by DNA direct sequencing. We identified 12 LDLR variants in 13 FH probands. Importantly, we first reported two unique mutations (c.2000_2000 delG/p.C667LfsX6 and c.605T>C/p.F202S) in LDLR gene. Our discoveries expand the spectrum of LDLR mutations and contribute to the genetic diagnosis and counseling for FH patients.
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Acknowledgments
We thank the patients and their families for participating in this study. We thank the Center of Clinical Gene Diagnosis and Therapy of the State Key Laboratory of Medical Genetics of China for technical assistance. This study was supported by the National Natural Science Foundation of China (81370394), the National Basic Research Program of China (973 Program) (2012CB517900), and the Fundamental Research Funds for Central Universities of Central South University (2014zzts284, 2014zzts086).
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Liang-liang Fan and Min-jie Lin contributed equally to this work.
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Fan, Ll., Lin, Mj., Chen, Yq. et al. Novel Mutations of Low-Density Lipoprotein Receptor Gene in China Patients with Familial Hypercholesterolemia. Appl Biochem Biotechnol 176, 101–109 (2015). https://doi.org/10.1007/s12010-015-1554-x
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DOI: https://doi.org/10.1007/s12010-015-1554-x