Abstract
Familial Hypercholesterolemia is an autosomal, dominant genetic disorder associated with premature cardiovascular disease (CVD). Mutations in the LDLR, APOB, and PCSK9 genes cause the FH phenotype, but in 20% of FH patients, mutations in other genes cause FH. In this regard, we investigated the genetic basis of an Autosomal Dominant Hypercholesterolemia (ADH) phenotype in an Iranian family via next-generation exome sequencing with a panel of hyperlipidemia. We report the first case of FH in an Iranian family due to a mutation in the APOE gene. A 10-year-old female was referred to our genetic clinic with a family history of hypercholesterolemia and high cholesterol level at the age of 3. Evaluation of the lipid profile showed the off total cholesterol of 338 mg/dl, low-density lipoprotein cholesterol (LDL-C of 247 mg/dl(. We identified a mutation in the APOE gene, c.500_502del /p. Leu167del confirmed co-segregation in three individuals of the family from three generations. This in-frame mutation identified here, the first report in Iran, confirms previous reports that ADH can be caused by mutations within the APOE gene and strongly introduces it as the 4th gene that must be checked in the genetic investigating of FH.