Clinical and genetic analysis of a family diagnosed with familial hypobetalipoproteinemia in which the proband was diagnosed with diabetes mellitus

Abstract Objective To perform clinical and genetic analysis of a family with familial hypobetalipoproteinemia in which the proband had been diagnosed with diabetes mellitus. Methods Direct sequencing was performed on candidate genes such as APOB , PCSK9 , and ANGPTL3 . The effect of the mutant gene on lipid profile was investigated using biochemical methods. Results A novel mutation Y344S in ANGPTL3 was identified but no variants were found in PCSK9 or APOB . Lipid profiles showed the levels of TG, TC, and LDL-C to be significantly lower in Y344S carriers than in non-carriers in this family. The levels of HDL-C and plasma concentrations of ANGPTL3 showed no significant differences. Western blot analysis revealed that the mutant ANGPTL3 proteins could not be secreted into the medium. Conclusion A novel mutation Y344S was found in ANGPTL3 gene in two diabetic patients with familial hypobetalipoproteinemia. The family study and genetic analysis suggest that this set of gene mutation may be a genetic basis for the lipid phenotypes, and may become a vascular protective factor in the probands with high risk of atherosclerosis.