Summary
While genetic testing can help identify the cause of inherited lipid disorders like familial hypercholesterolemia (FH), guide management, and identify at risk family members, it is often underutilized. To provide further support for testing in this patient population, we reviewed results from 1,041 patients who were suspected of having a monogenic lipid disorder and underwent the Blueprint Genetics Hyperlipidemia (broad) or Hyperlipidemia core (targeted) nextgeneration sequencing (NGS) panel that included both sequencing and high-resolution copy number variant (CNV) analysis. Key findings are that
- Overall, 28% of patients received an informative result
- CNVs accounted for 14% of informative results; over one- third of these were single- exon deletions in the LDLR gene
- The FH-focused panel had a higher yield than the broader panel (43% vs 24%)
These results highlight the value of NGS panel testing patients with suspected monogenic lipid disorders, and the importance of high-resolution CNV analysis given the proportion of informative cases explained by small CNVs.
Authors:
Julie Hathaway, Johanna Huusko, Saija Ahonen, Johanna Tommiska, Kimberly Gall, Allison Sluyters, Alicia Scocchia, Khalida Liaquat, Emily Partack, Janica Djupsjöbacka, Mikko Muona, Inka Saarinen, Eija Seppälä, Tiia Kangas-Kontio, Lotta Koskinen, Pertteli Salmenperä, Samuel Myllykangas, Juha Koskenvuo
References:
1.Sturm AC, Knowles JW, Gidding SS, Ahmad ZS, Ahmen CD, et al. Clinical genetic testing for familial hypercholesterolemia: JACC scientific expert panel. J Am Coll Cardiol. 2018. Aug 7;72(6):662 680. doi:10.106/j.jacc.2018.05.044
2.Kramer AI, Christian S, Bartels K,Vaizman N, Hegele RA, Brunham LR. Genetic Testing for Familial Hypercholesterolemia: The Current State of Its Implementation in Canada. CJC Open. 2024;6(11):1395-1402. Published 2024 Aug 14. doi:10.1016/j.cjco.2024.08.005