Screening and verifying the mutations in the LDLR and APOB genes in a Chinese family with familial hypercholesterolemia

Lipids in Health and Disease, 2023 · DOI: https://doi.org/10.1186/s12944-023-01935-8 · Published: October 2, 2023

Cardiovascular Science Endocrinology Genetics

Simple Explanation

Familial hypercholesterolemia (FH) is a genetic disorder leading to high cholesterol levels. This study aimed to identify the genetic mutations causing FH in a Chinese family. The researchers found a novel mutation in the LDLR gene and variants in the APOB gene that, together, contribute to the severity of FH in the studied family. Treatment with a PCSK9 inhibitor was not effective in reducing lipid levels in the proband and his brother, suggesting that genetic testing is crucial for determining suitable treatment options.

Study Duration

1 year

Participants

Proband and his brother

Evidence Level

Not specified

Key Findings

1
A novel frameshift insertion (c.497delinsGGATCCCCCAGCTGCATCCCCCAG: p. Ala166fs) was identified in the LDLR gene, preventing proper expression of LDLR on the cell membrane.
2
Variants in the APOB gene, particularly in exons 26 and 29, contribute to the severe clinical symptoms observed in the proband.
3
The proband's insensitivity to PCSK9 inhibitors can be attributed to the combined effects of LDLR and APOB variants.

Research Summary

This study identified a novel frameshift insertion in the LDLR gene and several variants in the APOB gene in a Chinese family with familial hypercholesterolemia. The cumulative effect of these genetic variants likely contributes to the severe clinical symptoms observed in the proband, who also showed insensitivity to PCSK9 inhibitor therapy. The findings underscore the importance of genetic testing for identifying primary pathogenic genes and establishing effective treatment approaches for patients with severe FH symptoms.

Practical Implications

Personalized Treatment

Genetic testing can guide the selection of appropriate therapies for FH patients, especially those with complex genetic profiles.

Novel Therapeutic Targets

The identification of specific APOB variants may lead to the development of new therapeutic interventions for lowering lipid levels in FH.

Improved Diagnosis

The study emphasizes the need for early and accurate genetic diagnosis of FH to prevent premature cardiovascular disease.

Study Limitations

1
Further investigations are needed to fully understand the expression and translation of the new mutation in LDLR.
2
There is a lack of direct evidence linking the numerous APOB variants observed in this family to their pathogenicity.
3
The clinical significance of these newly discovered variants requires epidemiological data, which were not available in this study.

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