Skip to main content

Advertisement

SpringerLink
Log in

Familial hypercholesterolemia in an Iranian family due to a mutation in the APOE gene (first case report)

  • Case report
  • Published:
Journal of Diabetes & Metabolic Disorders Aims and scope Submit manuscript

Abstract

Familial Hypercholesterolemia is an autosomal, dominant genetic disorder associated with premature cardiovascular disease (CVD). Mutations in the LDLR, APOB, and PCSK9 genes cause the FH phenotype, but in 20% of FH patients, mutations in other genes cause FH. In this regard, we investigated the genetic basis of an Autosomal Dominant Hypercholesterolemia (ADH) phenotype in an Iranian family via next-generation exome sequencing with a panel of hyperlipidemia. We report the first case of FH in an Iranian family due to a mutation in the APOE gene. A 10-year-old female was referred to our genetic clinic with a family history of hypercholesterolemia and high cholesterol level at the age of 3. Evaluation of the lipid profile showed the off total cholesterol of 338 mg/dl, low-density lipoprotein cholesterol (LDL-C of 247 mg/dl(. We identified a mutation in the APOE gene, c.500_502del /p. Leu167del confirmed co-segregation in three individuals of the family from three generations. This in-frame mutation identified here, the first report in Iran, confirms previous reports that ADH can be caused by mutations within the APOE gene and strongly introduces it as the 4th gene that must be checked in the genetic investigating of FH.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Wonderling D, Umans-Eckenhausen MA, Marks D, Defesche JC, Kastelein JJ, Thorogood M, editors. Cost-effectiveness analysis of the genetic screening program for familial hypercholesterolemia in The Netherlands. Seminars in vascular medicine; 2004: Copyright© 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

  2. Austin MA, Hutter CM, Zimmern RL, Humphries SE. Familial hypercholesterolemia and coronary heart disease: a HuGE association review. Am J Epidemiol. 2004;160(5):421–9.

    Article  Google Scholar 

  3. van Aalst-Cohen ES, Jansen AC, Tanck MW, Defesche JC, Trip MD, Lansberg PJ, et al. Diagnosing familial hypercholesterolaemia: the relevance of genetic testing. Eur Heart J. 2006;27(18):2240–6.

    Article  Google Scholar 

  4. Movahedian A, Ghannadi A, Vashirnia M. Hypocholesterolemic effects of purslane extract on serum lipids in rabbits fed with high cholesterol levels. Int J Pharmacol. 2007;3(3):285–9.

    Article  Google Scholar 

  5. Awan Z, Choi HY, Stitziel N, Ruel I, Bamimore MA, Husa R, et al. APOE p.Leu167del mutation in familial hypercholesterolemia. Atherosclerosis. 2013;231(2):218–22.

    Article  CAS  Google Scholar 

  6. Marduel M, Ouguerram K, Serre V, Bonnefont-Rousselot D, Marques-Pinheiro A, Erik Berge K, et al. Description of a large family with autosomal dominant hypercholesterolemia associated with the APOE p.Leu167del mutation. Hum Mutat. 2013;34(1):83–7.

  7. Okorodudu DE, Crowley MJ, Sebastian S, Rowell JV, Guyton JR. Inherited lipemic splenomegaly and the spectrum of apolipoprotein E p.Leu167del mutation phenotypic variation. J Clin Lipidol. 2013;7(6):566–72.

    Article  Google Scholar 

  8. Subramani KS, Kolhari VB, Manjunath CN, Bhairappa S. Familial hypercholesterolaemia presenting with coronary artery disease in a young patient. BMJ Case Rep 2013;2013:bcr2013008718.

  9. Herz J, Chen Y. Reelin, lipoprotein receptors and synaptic plasticity. Nat Rev Neurosci. 2006;7(11):850–9.

    Article  CAS  Google Scholar 

  10. Cenarro A, Etxebarria A, de Castro-Oros I, Stef M, Bea AM, Palacios L, et al. The p.Leu167del mutation in APOE gene causes autosomal dominant hypercholesterolemia by Down-regulation of LDL receptor expression in hepatocytes. J Clin Endocrinol Metab. 2016;101(5):2113–21.

    Article  CAS  Google Scholar 

  11. Henderson R, O'Kane M, McGilligan V, Watterson S. The genetics and screening of familial hypercholesterolaemia. J Biomed Sci. 2016;23:39.

    Article  Google Scholar 

  12. https://genetics.bwh.harvard.edu/pph2. Wsh. PolyPhen-2 prediction of functional effects of human nsSNPs accessed January 2013.

  13. Nguyen TT, Kruckeberg KE, O'Brien JF, Ji ZS, Karnes PS, Crotty TB, et al. Familial splenomegaly: macrophage hypercatabolism of lipoproteins associated with apolipoprotein E mutation [apolipoprotein E (delta149 Leu)]. J Clin Endocrinol Metab. 2000;85(11):4354–8.

    CAS  PubMed  Google Scholar 

  14. Faivre L, Saugier-Veber P, Pais de Barros JP, Verges B, Couret B, Lorcerie B, et al. Variable expressivity of the clinical and biochemical phenotype associated with the apolipoprotein E p.Leu149del mutation. Eur J Hum Genet: EJHG. 2005;13(11):1186–91.

    Article  CAS  Google Scholar 

  15. Rahalkar AR, Wang J, Sirrs S, Dimmick J, Holmes D, Urquhart N, et al. An unusual case of severe hypertriglyceridemia and splenomegaly. Clin Chem 2008;54(3):606-10; discussion 10-1.

  16. Mohd Nor NS, Al-Khateeb AM, Chua Y-A, Mohd Kasim NA, Mohd NH. Heterozygous familial hypercholesterolaemia in a pair of identical twins: a case report and updated review. BMC Pediatr. 2019;19(1):106.

    Article  Google Scholar 

  17. Wiegman A, Gidding SS, Watts GF, Chapman MJ, Ginsberg HN, Cuchel M, et al. Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. Eur Heart J. 2015;36(36):2425–37.

    Article  Google Scholar 

  18. Moorjani S, Roy M, Gagne C, Davignon J, Brun D, Toussaint M, et al. Homozygous familial hypercholesterolemia among French Canadians in Quebec Province. Arteriosclerosis (Dallas, Tex). 1989;9(2):211–6.

    CAS  Google Scholar 

  19. Wintjens R, Bozon D, Belabbas K, MBou F, Girardet JP, Tounian P, et al. Global molecular analysis and APOE mutations in a cohort of autosomal dominant hypercholesterolemia patients in France. J Lipid Res. 2016;57(3):482–91.

    Article  CAS  Google Scholar 

  20. Versmissen J, Oosterveer DM, Yazdanpanah M, Defesche JC, Basart DC, Liem AH, et al. Efficacy of statins in familial hypercholesterolaemia: a long term cohort study. BMJ (Clinical research ed). 2008;337:a2423.

    Article  Google Scholar 

  21. Marks D, Wonderling D, Thorogood M, Lambert H, Humphries SE, Neil HA. Cost effectiveness analysis of different approaches of screening for familial h. BMJ (Clinical research ed). 2002;324(7349):1303.

    Article  Google Scholar 

Download references

Acknowledgments

The authors thank the proband family and the nurses and staff of the Genetic clinic.

Author information

Authors and Affiliations

  1. Department of Pediatric Endocrinology and Metabolism, Emam Ali Hospital, Alborz University of Medical Sciences, Karaj, Iran

    Shahab Noorian

  2. Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Rezvan Razmandeh

  3. Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran

    Roshanak Jazayeri

  4. Department of Genetics, Faculty of Medicine, Alborz University of Medical Sciences, Karaj, Iran

    Roshanak Jazayeri

Authors
  1. Shahab Noorian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rezvan Razmandeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roshanak Jazayeri
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Roshanak Jazayeri.

Ethics declarations

Conflicting interests

The authors declared no potential conflicts of interest with respect to this article.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Noorian, S., Razmandeh, R. & Jazayeri, R. Familial hypercholesterolemia in an Iranian family due to a mutation in the APOE gene (first case report). J Diabetes Metab Disord 21, 1201–1205 (2022). https://doi.org/10.1007/s40200-022-01007-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40200-022-01007-1

Keywords

Search

Navigation