Effect of mutation in exon.4 of the LDL Receptor gene (LDLR) in familial hypercholesterolemia

Family Hypercholesterolemia (FH) is a common autosomal dominant genetic disorder that results from high levels of low-density lipoprotein cholesterol (LDL) and increases the risk of early-onset cardiovascular disease in men and women(1).As cardiovascular disease appears in heterozygous patients under the age of 20 years and in heterozygous patients under age 50(2).The incidence of this disease is 1 in 200 to 500 people in the world. It is not a rare disease, but it is fortunate to be diagnosed, and its treatment is possible. Early diagnosis and treatment can decrease the risk of atherosclerotic cardiovascular disease caused by the FH(3).Diagnosis can be done based on clinical criteria (including LDL, cholesterol and family history) or DNA testing. Over the past decades, cascade screening program has been conducted in many countries and regions that have led to the identification of a large number of these patients(3). Most of the single-gene causes of FH-induced mutations in one of the three LDLR, APOB, and PSCK9 genes, of which about 90% occur in the LDLR gene and more than 1200 different mutations are detected (4). So far, all of the exons of the LDL receptor gene have been found to have various types of mutations associated with the disease(5–7), but because of the high percentage of mutations in exon 4 in the studies performed so far in the world(6,8–10), this study examines the mutations observed in this exon in patients with familial hypercholesterolemia.