Familial Hypercholesterolemia in Iran: A Novel Frameshift Mutation in Low Density Lipoprotein Receptor (LDLR) Gene

Familial hypercholesterolemia (FH) is an autosomal trait, which is caused by mutations in Low Density Lipoprotein Receptor (LDLR) gene. FH penetrance is about 100% and worldwide prevalence for heterozygous subjects is almost 1 in 500 and for homozygous 1 in 1,000,000. The patients are at risk of premature coronary heart disease (CHD) due to defective LDLR and hence cholesterol metabolism disorder. The aim of this study was identifying genotype of possible mutation in an Iranian FH patient. Promoter and all 18 exons including exon-intron boundaries of LDLR gene were scanned. Polymerase chain reaction - single strand conformation polymorphism (PCRSSCP) was used as mutation scanning method. DNA sequencing was used to identify any nucleotide change(s). A new frameshift mutation (660-661InsCC) was found in proband. This mutation causes a truncated, non-functional protein, which results in hypercholesterolemia. The mutation can be screened in proband''s relatives to find other FH patients.