Genetic And Phenotype Study In A Family With Familial Hypercholesterolemia

ObjectiveFamilial hypercholesterolemia(FH) and familial defective apolipoprotein B-100 (FDB) are autosomal codominant diseases characterized by elevated LDL cholesterol levels and premature coronary artery disease.Mutations of the LDL-receptor and apolipoprotein B genes,which affect the binding domains of their protein products, are the causal defects.Securing the diagnosis of these conditions by molecular assays is important because it mandates early intervention for coronary risk reduction..The purpose of this study is to investigate the low density lipoprotein receptor(LDLR)gene and apolipoprotein B gene mutation in a Chinese family with familial hypercholesterolemia(FH) and make a discussion on the relationship between genotype and phenotype.MethodsAfter physical examination,the the kindreds underwent ECG and ultrasound checks.Blood samples were tested for lipid profiles.The promoter and all eighteen exons of LDLR gene were investigated by using PCR and agarose gel electrophoresis in combination with DNA sequence analysis.The results were compared with the normal sequences in GenBank and FH database(www.ucl.ac uk/fh ) to find mutations.In addition,the apolipoprotein B100 gene for known mutations(R3500Q,R3531C,R3501W and R3480W)that cause familial defective ApoB100(FDB)was also tested using the same method.ResultsA novel homozygous G＞A mutation at the 1581bp of exon 10 was detected in the proband and his siblings.It cause a substitution of amimo acid Glu to Gly at codon 496.A novel heterozygous G＞A mutation at the 1581bp of exon 10 was detected in his parents.No mutations of R3500Q,R3531C,R3501W and R3480W of ApoB100 were observed.ECGs were normal.Atherosclerosis were found in all family members by ultrasound checks. ConclusionsThe homozygous G＞A mutation at the 1581bp of exon 10 was first determined in our country.The change of amino acid Glu to Gly is responsible for FH of the family. The type of the gene mutation was not found in the GenBank.It's a new type of LDLR mutation.