Study Of Clinical Phenotype And LDL-R Gene Mutation In A Familial Hypercholesterolemia Family

Objective:To investigate the relationship between the clinical manifestation and mutation of low-density lipoprotein receptor(LDL-R)gene in a familial hypercholesterolemia(FH)Family,so as to discuss the pathogenesis of FH.Methods:The proband and her family members were selected to undergo physical examination,lipid level test,electrocardiography and cardiac ultrasound.Pedigree analysis was carried out based on family investigation.The promoter and the 18 exons of LDL-R gene were amplified by PCR;DNA sequencing was used to detect mutation.Amplified Apo B100 gene fragments by PCR to determin whether there existed familial defective apolipoprotein B(FDB).Results:A total of 8 people of 3 generations were investigated.Parents of proband were consanguineous marriage.The proband and her younger brother,father,mother,grandmothers and second uncle were FH patients.Their serum total cholesterol were18.98?8.69?7.51?7.36?11.64?9.24?9.57mmol/L.In addition to the clinical diagnosis of the proband was homozygous,the rest were heterozygous.The genetic pattern of this family was consistent to autosomal dominant inheritance trait.DNA sequencing ruled out the mutation of Apo B100 gene fragments,but LDL-R variation was identified(exon2;c.97C>T,p.(Q12X)).The mutation of the proband was homozygous,her younger brother,father,mother were heterozyous.Conclusion:1.The proband and his younger brother,father,mother,grandmothers,second uncle were all diagnosed with FH by clinical manifestation,physical examination,blood lipid determination and ultrasound examination,and the proband had reached the clinical diagnosis of homozygous FH,most members had varying degrees of atherosclerosis;2.There was no mutation of ApoB100 gene in thisfamily,and the possibility of FDB was excluded;3.The proband,her younger brother and parents have the same mutation,the Q12 X mutation in exon 2 of LDL-R gene,which might be the key mutation that cause FH in this pedigree;4.The clinical manifestations of FH were difference,and influenced by both genetic and environmental factors.