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Review
. 2024 Feb 26;15(3):297.
doi: 10.3390/genes15030297.

Genetic Counseling and Genetic Testing for Familial Hypercholesterolemia

Hayato Tada  1 , Masa-Aki Kawashiri  2 , Atsushi Nohara  3 , Tomoko Sekiya  4 , Atsushi Watanabe  4 , Masayuki Takamura  1
Affiliations
Review

Genetic Counseling and Genetic Testing for Familial Hypercholesterolemia

Hayato Tada et al. Genes (Basel). .

Abstract

Familial hypercholesterolemia (FH) is one of the most common autosomal codominant Mendelian diseases. The major complications of FH include tendon and cutaneous xanthomas and coronary artery disease (CAD) associated with a substantial elevation of serum low-density lipoprotein levels (LDL). Genetic counseling and genetic testing for FH is useful for its diagnosis, risk stratification, and motivation for further LDL-lowering treatments. In this study, we summarize the epidemiology of FH based on numerous genetic studies, including its pathogenic variants, genotype-phenotype correlation, prognostic factors, screening, and usefulness of genetic counseling and genetic testing. Due to the variety of treatments available for this common Mendelian disease, genetic counseling and genetic testing for FH should be implemented in daily clinical practice.

Keywords: LDL; familial hypercholesterolemia; genetic counseling; genetic testing; genetics.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Monogenic, oligogenic, and polygenic FH. Monogenic FH is caused by a rare variant with a large effect size. Oligogenic FH is caused by a rare variant with a large effect size and rare variant/s with moderate effect sizes. Polygenic FH is caused by multiple common variants with small effect sizes.
Figure 2
Figure 2
Impact of FH variants and clinical signs of FH on CAD. The 2 × 2 matrix represents the odds ratio for CAD wherein individuals without the FH variant and clinical signs of FH are used as a reference.
Figure 3
Figure 3
Prognosis of patients with FH according to genotype. Red: patients without pathogenic variants. Green: patients with missense variants. Blue: patients with protein-truncating variants.
Figure 4
Figure 4
Schematic of the Gentle-FH trial.
Figure 5
Figure 5
Primary endpoint (changes in LDL cholesterol) of the Gentle-FH trial. Purple: intervention group. Blue: control group.
See this image and copyright information in PMC

References

    1. Fularski P., Hajdys J., Majchrowicz G., Stabrawa M., Młynarska E., Rysz J., Franczyk B. Unveiling Familial Hypercholesterolemia-Review, Cardiovascular Complications, Lipid-Lowering Treatment and Its Efficacy. Int. J. Mol. Sci. 2024;25:1637. doi: 10.3390/ijms25031637. - DOI - PMC - PubMed
    1. Brandts J., Ray K.K. Familial hypercholesterolemia: JACC focus Seminar 4/4. J. Am. Coll. Cardiol. 2021;78:1831–1843. doi: 10.1016/j.jacc.2021.09.004. - DOI - PubMed
    1. van den Bosch S.E., Corpeleijn W.E., Hutten B.A., Wiegman A. How genetic variants in children with familial hypercholesterolemia not only guide detection, but also treatment. Genes. 2023;14:669. doi: 10.3390/genes14030669. - DOI - PMC - PubMed
    1. Beheshti S.O., Madsen C.M., Varbo A., Nordestgaard B.G. Worldwide prevalence of familial hypercholesterolemia: Meta-analyses of 11 million subjects. J. Am. Coll. Cardiol. 2020;75:2553–2566. doi: 10.1016/j.jacc.2020.03.057. - DOI - PubMed
    1. Raal F.J., Rosenson R.S., Reeskamp L.F., Hovingh G.K., Kastelein J.J.P., Rubba P., Ali S., Banerjee P., Chan K.C., Gipe D.A., et al. Evinacumab for homozygous familial hypercholesterolemia. N. Engl. J. Med. 2020;383:711–720. doi: 10.1056/NEJMoa2004215. - DOI - PubMed

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