Clinical Significance Of LDL-R Gene Original Mutation In A Familial Hypercholesterolemia Patient

ObjectiveFamilial hypercholesterolemia(FH) is an inherited autosomal dominant disorder of lipoprotein metabolism caused by mutations in the LDL-R gene. It causes a rise in LDL-C levels and predisposes to the development of atherosclerosis. The objective of our study is to use the molecule biology technique,such as PCR,SSCP and so on,which can find the mutation site in the LDL-R gene of the FH constellation. We analyze LDL-R function using FCM. In addition we will discuss the relationship in the phenotype and the LDL-R gene mutation type in FH.MethodsWe studied a FH family, which was diagnosed by clinical features and blood lipid tests. The proband was also applied with cardiovascular ultrasound. Lymphocytes and DNA were isolated from the whole blood of the health adult and the patients. We analyzed LDL-R function using FCM. Apo B100 gene Q3500R,R3531C and R3501W point mutation was detected by PCR and sequencing. 21 segments covered the promotor and the whole 18 LDL-R gene exons were amplified by PCR with the same reaction volume and cycle parameter. We analysed the segments by SSCP technique. LDL-R point mutation was detected by PCR and sequencing. The result of sequencing compared to Genebank, and authenticate it in 100 normal people. ResultsWe find the proband have sign of CAD. Electrocardiogram displayⅠ,avL,Ⅴ5 andⅤ6 ST segment drawdown. The LDL-R binding and internalization activity on the lymphocytes of the FH proband is significantly lower than that of the normal. The FH proband has no mutation in Apo B100 gene Q3500R,R3531C and R3501W site. We find a novel heterozygosis T→C mutation in the LDL-R extron 4 was detected in the FH proband.we certified it is a new morbigenous mutation.Conclusions1. The proband is dignosised CAD. He has severe sign of As.2. The FH patient has no mutation in Apo B100 gene;3. A novel homozygosis T→C mutation in the LDL-R gene was detected in the FH patient.4. Function of LDL receptor in the FH homozygote are at a notbaly low level, it relates probably to the mutation of the FH patient.5. The patient has a high cholesterol level, which probably because the mutation leading to LDL-R activity degression, it is perhaps reason of CAD occurrence .