Identification and 3D architecture analysis of the LIPC gene mutation in a pedigree with familial hypercholesterolemia-like phenotype.
10.3760/cma.j.cn112148-20230601-00321
- VernacularTitle:一个家族性高胆固醇血症样表型相关LIPC突变位点的鉴定与三维结构分析
- Author:
Hang ZHANG
1
;
Fang Yuan LI
2
;
Yu HAO
3
;
Xu Min WANG
4
;
Ju ZHANG
3
;
Ya Luan MA
5
;
Hui ZENG
2
;
Jie LIN
1
Author Information
1. Department of Atherosclerosis, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, China.
2. Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Peking University Ditan Teaching Hospital, Beijing 100015, China.
3. Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China.
4. College of Life Sciences, Yantai University, Yantai 264005, China.
5. Institute of Basic Medical Theory of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.
- Publication Type:Journal Article
- MeSH:
Humans;
Male;
Hyperlipoproteinemia Type II/genetics*;
Lipase/genetics*;
Lipids;
Mutation;
Pedigree;
Phenotype;
Proteins
- From:
Chinese Journal of Cardiology
2023;51(7):716-721
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To identify and analyze 3D architecture of the mutational sites of susceptible genes in a pedigree with familial hypercholesterolemia-like phenotype (FHLP). Methods: This is a case series study. A pedigree with suspected familial hypercholesterolemia was surveyed. The proband admitted in Beijing Anzhen Hospital in April 2019. Whole-exome sequencing was performed to determine the mutational sites of susceptible genes in the proband. Polymerase chain reaction (PCR) sequencing was used to verify the pathogenic variant on proband's relatives. The structural and functional changes of the proteins were analyzed and predicted by Discovery Studio 4.0 and PyMol 2.0. Results: The patients in the pedigree showed abnormal lipid profiles, especially elevated levels of total cholesterol(TC). The genetic screening detected the c.1330C>T SNP in the exon 8 of lipase C (LIPC) gene, this mutation leads to an amino acid substitution from arginine to cysteine at position 444 (Arg444Cys), in the proband and proband's father and brother. In this family, members with this mutation exhibited elevated TC, whereas lipid profile was normal from the proband's mother without this mutation. This finding indicated that LIPC: c.1330C>T mutation might be the mutational sites of susceptible genes. The analysis showed that Arg444Cys predominantly affected the ligand-binding property of the protein, but had a limited impact on catalytic function. Conclusion: LIPC: c.1330C>T is a new mutational site of susceptible genes in this FHLP pedigree.
