OBJECTIVE: To screen for LDLR gene mutations in 9 patients with familial hypercholesterolemia (FH). METHODS: All exons of the LDLR gene and flanking intronic sequences were amplified by PCR and subjected to automatic DNA sequencing. For patients with homozygous or compound heterozygous mutations, parental DNA sequencing or T cloning sequencing was carried out to determine the parental origin of the mutant alleles. RESULTS: Direct sequencing of PCR products revealed 8 LDLR variants in 7 patients, which included c.259T>G, c.513delC, c.530C>T, c.682G>T, c.763C>T, c.1187-10G>A, c.1948delG, and c.1730G>A, among which c.1948delG was novel. Four patients have carried heterozygous mutations, two carried homozygous mutations, and one carried compound heterozygous mutations. The patients with biallelic mutations presented with a more severe phenotype compared those carrying heterozygous mutations. CONCLUSION LDLR mutations were identified in 7 out of 9 patients with FH. Among the 8 identified LDLR mutations, c.1948delG was firstly reported. Above findings have expanded the mutation spectrum of LDLR gene.
DNA Mutational Analysis ; Genetic Testing ; Humans ; Hyperlipoproteinemia Type II ; genetics ; Mutation ; Phenotype ; Receptors, LDL ; genetics