Identification of a Novel Frame Shift Mutation of the LDL Receptor Gene Causing Familial Hypercholesterolemia in Omani Family*

Abstract

Synopsis: Familial hypercholesterolemia (FH) is an autosomal dominant disease caused commonly by mutation in the low-density lipoprotein receptor (LDLR) gene. It is characterized by a high concentration of low-density lipoprotein cholesterol (LDL-C), and premature coronary artery disease. Purpose: In this study, we report a novel frame shift deletion mutation of the LDL receptor gene in Omani family. Methods: Five patients from the family were screened for mutations in the LDLR gene using direct sequencing of the promoter and 18 exons. Results: The probandwas a 10-year-old girlwith total cholesterol of 23.2mmol/L, LDL-C of 22.1mmol/L, triglyceride 0.8 mmol/L, HDL-C0.74mmol/L, ApoB4.5 g/L, Lpa 1110mg/L with tendon xanthomas and measured carotid intima media thickness (CIMT) of 1.05 mm. Both the parents and the other two sisters’ ages (13 and 15 years) had high LDL-C 7.1, 6.4, 5.2, and 6.4 mmol/L, respectively. The direct sequencing of the LDL-receptor gene revealed a homozygous frame shift deletion (272delG) of exon 3 in the proband. The parents and the two sisters were heterozygous for this variant. Conclusions: This study identified a novel framshift deletion mutation (272delG) in exon 3 of the LDL receptor gene that causes FH in this Omani family. In Oman the prevalence of FH is not known; therefore, more genetic studies are needed to characterize the molecular basis of FH.