Identification of a novel nonsense variant c.1332dup, p.(D445) in the LDLR gene that causes familial hypercholesterolemia

Familial hypercholesterolemia (FH) is an autosomal dominant disease predominantly caused by a mutation in the low-density lipoprotein receptor ( LDLR ) gene. Here, we describe two severely affected FH patients who were resistant to statin therapy and were managed on an apheresis program. We identified a novel duplication variant c.1332dup, p.(D445*) at exon 9 and a known silent variant c.1413A>G, p.(=), rs5930, NM_001195798.1 at exon 10 of the LDLR gene in both patients. Cardiac disease: Finding genes for high cholesterol levels A novel gene variant associated withfamilial hypercholesteremia (FH) has been identified in two patients from Saudi Arabia. The patients have the same mutation in the low-density lipoprotein receptor ( LDLR ) gene, which codes for a protein that removes LDL or „bad” cholesterol from the blood. LDL accumulation causes hypercholesterolemia, which increases the risk of cardiac disease. Although FH is prevalent in Saudi Arabia, no studies of the underlying genetics had been conducted there. Faisal A Al-Allaf (Umm Al-Qura University) and Abdullah Alashwal (KFSH&RC) and co-workers in Saudi Arabia sequenced the LDLR genes of two patients with FH, and identified a novel mutation that results in production of a non-functional protein likely to be rapidly degraded in cells. FH can be confused with non-genetic high cholesterol levels. Identifying genetic markers for FH can greatly improve diagnosis and treatment.