Department of Human Genetics, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands.
Department of Paediatrics, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands.
Genes (Basel). 2021 Jul 29;12(8):1168. doi: 10.3390/genes12081168.
The genetic screening program for familial hypercholesterolemia (FH) in the Netherlands, which was embraced by the Dutch Ministry of Health from 1994 to 2014, has led to twenty years of identification of at least 1500 FH cases per year. Although funding by the government was terminated in 2014, the approach had proven its effectiveness and had built the foundation for the development of more sophisticated diagnostic tools, clinical collaborations, and new molecular-based treatments for FH patients. As such, the community was driven to continue the program, insurance companies were convinced to collaborate, and multiple approaches were launched to find new index cases with FH. Additionally, the screening was extended, now also including other heritable dyslipidemias. For this purpose, a diagnostic next-generation sequencing (NGS) panel was developed, which not only comprised the culprit , , and genes, but also 24 other genes that are causally associated with genetic dyslipidemias. Moreover, the NGS technique enabled further optimization by including pharmacogenomic genes in the panel. Using such a panel, more patients that are prone to cardiovascular diseases are being identified nowadays and receive more personalized treatment. Moreover, the NGS output teaches us more and more about the dyslipidemic landscape that is less straightforward than we originally thought. Still, continuous progress is being made that underlines the strength of genetics in dyslipidemia, such as discovery of alternative genomic pathogenic mechanisms of disease development and polygenic contribution.
荷兰的家族性高胆固醇血症（FH）基因筛查计划于 1994 年至 2014 年被荷兰卫生部采纳，该计划每年至少发现 1500 例 FH 病例。尽管政府在 2014 年停止了资助，但该方法已被证明是有效的，并为开发更复杂的诊断工具、临床合作以及 FH 患者的新分子治疗方法奠定了基础。因此，社区推动继续开展该计划，保险公司也被说服进行合作，并采取多种方法寻找新的 FH 索引病例。此外，筛查范围扩大，现在还包括其他遗传性血脂异常。为此，开发了一种诊断性下一代测序（NGS）面板，该面板不仅包含罪魁祸首、和基因，还包含 24 个与遗传性血脂异常相关的其他基因。此外，NGS 技术通过在面板中包含药物基因组学基因，实现了进一步的优化。使用这样的面板，现在可以识别出更多易患心血管疾病的患者，并为他们提供更个性化的治疗。此外，NGS 输出结果让我们越来越了解血脂异常的情况，其复杂程度超出了我们的最初设想。尽管如此，不断取得的进展突显了遗传学在血脂异常中的重要性，例如发现疾病发展的替代基因组发病机制和多基因贡献。
