ABSTRACT

Introduction: Familial hypercholesterolemia (FH) is a highly prevalent condition, predisposing individuals to premature cardiovascular disease and with a genetic basis more complex than initially thought. Advances in molecular technologies have provided novel insights into the role of next-generation-sequencing, the assessment and classification of newly found variants, the complex genotype-phenotype correlation, and the position of FH in the context of other dyslipidaemias.

Areas covered: Understanding the scope of genetic determinants of FH has expanded substantially. This article reviews the current literature on the complexity that comes with this incremental knowledge and highlights the added value of genetic testing as an addition to phenotypic diagnosis of FH. Moreover, we discuss the broad genetic basis of FH, with a focus on the three main FH genes, but we also pay attention to polygenic hypercholesterolemia as well as minor and modulator genes involved in FH.

Expert opinion: Both the availability and the need for genetic analysis of FH are on the rise as costs of sequencing continue to drop and new therapies require a genetic diagnosis for reimbursement. However, greater use of genetic testing requires more education of healthcare professionals, since molecular technologies will allow for rapid and accurate evaluation of large numbers of detected variants.

摘要

简介: 家族性高胆固醇血症 (FH) 是一种高度普遍的疾病，使个体易患过早心血管疾病，其遗传基础比最初想象的更复杂。分子技术的进步为下一代测序的作用、新发现的变异的评估和分类、复杂的基因型-表型相关性以及 FH 在其他血脂异常背景下的位置提供了新的见解。

涵盖的领域：了解 FH 遗传决定因素的范围已大大扩展。本文回顾了当前有关这种增量知识带来的复杂性的文献，并强调了基因检测作为 FH 表型诊断的附加值。此外，我们讨论了 FH 的广泛遗传基础，重点关注三个主要的 FH 基因，但我们也关注多基因高胆固醇血症以及与 FH 相关的次要基因和调节基因。

专家意见：随着测序成本持续下降，新疗法需要基因诊断才能报销，FH 基因分析的可用性和需求都在增加。然而，更多地使用基因检测需要对医疗保健专业人员进行更多的教育，因为分子技术将允许对大量检测到的变异进行快速准确的评估。