Screening of LDLR gene mutations in nine patients with familial hypercholesterolemia

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. Key words: Familial hypercholesterolemia; LDLR gene; Genetic testing; Mutation