Mutation analysis of low-density lipoprotein receptor gene in 3 patients with familial hypercholesterolemia in two generations
10.3724/SP.J.1008.2012.00445
- Author:
Hong WU
1
Author Information
1. Department of Cardiovasology, Changhai Hospital, Second Military Medical University
- Publication Type:Journal Article
- Keywords:
Genotype;
Hypercholesterolemia type II;
Low-density lipoprotein receptor;
Mutation
- From:
Academic Journal of Second Military Medical University
2012;33(4):445-448
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mutation of low-density lipoprotein receptor (LDL-R) gene in 3 patients with familial hypercholesterolemia (FH) in two generations, so as to discuss the pathogenesis of FH. Methods A 17-year-old patients was selected to undergo physical examination, lipid level test, electrocardiography, cardiac ultrasound and coronary artery angiography. Pedigree analysis was carried out based on family investigation. The promoter and the 18 exons of the LDL-R gene and the flank sequence were amplified by PCR; DNA sequencing was used to detect point mutation. Ninety normal subjects from the native place of the proband and 190 subjects from random population were taken as controls. Results Totally 28 members of 4 generations were examined. The proband, her elder sister and grandaunt had FH with xanthoma, and their total cholesterol (TC) levels were 18. 89 mmol/L, 15. 23 mmol/L, and 12. 89 mmol/L, respectively. Pedigree analysis showed that the genetic pattern of this family was consistent to autosomal dominant inheritance trait. DNA sequencing demonstrated that a G1448A substitution caused a nonsense mutation TGG to TAG in exon 10 of LDL-R gene, a Trp→462 stop mutation. The mutation of the proband, her older sister and grandaunt were homozygous, heterozygous and heterozygous, respectively. The same mutation was not detected in the family members from the proband' s father and people from control group. Conclusion The proband, her elder sister and grandaunt have the same mutation, the Trp→462 stop mutation in exon 10 of LDL-R gene, which might be the key mutation that causes FH in this pedigree.
