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

  • Xiaoli Wang
    Correspondence
    Corresponding author. Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Nanjing North Street, No 155, Shenyang 110001, PR China.
    Affiliations
    Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001, PR China
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  • Dongdong Wang
    Affiliations
    Department of Obstetrics and Gynecology of Shengjing Hospital, China Medical University, Shenyang 110001, PR China
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  • Zhongyan Shan
    Affiliations
    Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001, PR China
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      Highlights

      • A novel mutation Y344S in ANGPTL3 was identified in a family with familial hypobetalipoproteinemia.
      • Mutations in ANGPTL3 gene may have the phenotypic heterogeneity.
      • Loss-of-function in ANGPTL3 may become a vascular protective factor.

      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.

      Keywords

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