[A compound heterozygote family of familial hypercholesterolemia due to new mutations]

To investigate the molecular diagnosis method and possible molecular mechanism of the etiology of a hereditary genetic hypercholesterolemia family by scanning and analyzing the related genes of hereditary hypercholesterolemia in a clinically diagnosed proband and his family members.Molecular diagnosis was performed with PCR and then DNA sequencing of the promoter and 18 exons of low-density lipoprotein receptor (LDLR) gene and 3500 - 3531 fragment of apolipoprotein B-100 gene was carried out. The sequencing results were compared with the normal nucleotide sequence queried from the GeneBank database to discover the mutations.Familial defective apolipoprotein B-100 was excluded, as no mutation was detected in the apolipoprotein B 3500 - 3531 fragment. Two new point mutations were detected in the exon 4 of the proband's LDLR gene, they were heterozygous 685delA (Del A at 685) and 386AG. The sequencing in his parents and other family members showed that the two mutations were paternal origin (685delA) and maternal origin (386AG) respectively and should be located in different alleles of the proband.Molecular diagnosis in the family shows that the proband is a compound heterozygote and the newly detected LDLR gene mutations of 685delA and 386AG are the possible molecular etiological basis of the disease in this family.