Mutation analysis of candidate genes in familial hypercholesterolemia in an affected family in Alborz Province

Introduction: Familial Hypercholesterolemia (FH) is an autosomal, dominant genetic disorder that associated with premature cardiovascular disease (CVD). Mutations in the LDLR, APOB and PCSK9 genes cause the FH phenotype, but in a20% of FH patients, mutations in other genes cause FH.Methods: We investigated the genetic basis of an ADH phenotype in an Iranian family via next-generation exome sequencing with panel of hyperlipidemia. We performed sanger sequencing to confirm our result, and to evaluate co-segregation in the family.Results: We identified a mutation in the APOE gene, c.500_502del /p.Leu167del, confirmed with sanger sequencing, which was co-segregated in three individuals of the family from three generations. Conclusion: Because heritability and mutation are also influenced by various environmental factors including diet and other genes, performing routine tests to determine the level of LDL and cholesterol due to its high sensitivity and low profile for early diagnosis and adequate timely treatment are not adequate. And precise molecular testing is required because of the sensitivity and specificity of 100% to determine genes and common mutations and to screening the genetic cause of the disease and, consequently, the correct treatment. Extensive variation in the types of genes involved in FH and their mutations requires the necessity of regional testing and determining the prevalence of various mutations and then performing routine tests based on those types of mutations.This in-frame mutation identified here, which is 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 checking in genetic investigating of FH.

Keywords:

familial hyperchlosterolemia , APOE gene , mutation , cardio vascular disease , screening , next generation sequencing