A Homozygous Missense Variant in the APOB gene in Patients from Hypercholesterolemia Families

Familial hypercholesterolemia (FH) is an autosomal codominant, life-threatening inherited condition. FH is characterized by an increased blood level of low-density lipoprotein cholesterol (LDL-C). Patients with FH are at serious risk of developing premature atherosclerotic cardiovascular disease. Association of FH with genetic variants in three genes (APOB, LDLR, and PCSK9) is well established, however, the data related to mutation spectrum and prevalence of FH in Saudi population is largely missing. Here, we studied two Saudi families segregating FH in an autosomal dominant manner. All exons and intro-exons junctions of three candidate genes (APOB, LDLR, and PCSK9) were sequenced using Sanger approach. Data analysis identified variants in exon 14 (c.1853C>T; p.Ala618Val) and exon 29 (c.13013G>A; p.Ser4338Asn) of the APOB gene in both families. Both variants perfectly segregating with FH phenotype in families. The variant (c.13013G>A) is located in the well-established active site of apolipoprotein B, thus, it might influence the enzyme activity. In conclusion, we found homozygosity for variant in APOB in families segregating FH. This study expanded the mutational spectrum of APOB in FH. In addition, the present study provided additional evidence that supports the important involvement of apolipoprotein B dysregulation in Saudi FH patients.