Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
J Clin Lipidol. 2020 May-Jun;14(3):331-338. doi: 10.1016/j.jacl.2020.02.006. Epub 2020 Mar 2.
It is estimated that less than 10% of cases of familial hypercholesterolemia (FH) in the United States have been diagnosed. Low rates of diagnosis may in part be attributable to affected patients not meeting the clinical diagnostic criteria of the Dutch Lipid Clinic Network (DLCN), Simon Broome, or US MEDPED diagnostic criteria.
The objective of this study was to assess the utility of incorporating genetic testing into a patient's evaluation for FH.
We retrospectively reviewed patients seen in the Advanced Lipids Disorders Clinic at Johns Hopkins Hospital between January 2015 and May 2018. Between June 2018 and December 2018, patients were consented to a prospective registry. DLCN, Simon Broome, and MEDPED criteria were applied to each patient, before and after genetic testing. Genetic testing included sequencing and deletion duplication analysis of four genes (LDLR, PCSK9, APOB, and LDLRAP1).
The retrospective review and prospective study identified 135 adult probands who were seen in our clinic for evaluation of heterozygous FH. Twenty-nine individuals (21%) were heterozygous for a pathogenic or likely pathogenic monogenic variant. Before genetic testing, using the DLCN criteria, 35 (26%) individuals met criteria for a definite diagnosis of FH. Thirty patients (22%) met criteria using Simon Broome, and 29 (21%) patients met criteria using US MEDPED before genetic analysis. Depending on the criteria, incorporating genetic testing identified 11-14 additional patients with FH.
Incorporating genetic testing diagnosed almost 50% more patients with definite FH in comparison to classification solely on clinical grounds.
据估计，在美国，家族性高胆固醇血症（FH）患者中只有不到 10%得到确诊。低诊断率的部分原因可能是受影响的患者不符合荷兰脂质诊所网络（DLCN）、Simon Broome 或美国 MEDPED 诊断标准的临床诊断标准。
本研究旨在评估将基因检测纳入 FH 患者评估中的效用。
我们回顾性分析了 2015 年 1 月至 2018 年 5 月在约翰霍普金斯医院高级血脂异常诊所就诊的患者。在 2018 年 6 月至 2018 年 12 月期间，患者同意加入前瞻性注册研究。在进行基因检测之前和之后，我们分别使用 DLCN、Simon Broome 和 MEDPED 标准对每位患者进行评估。基因检测包括对四个基因（LDLR、PCSK9、APOB 和 LDLRAP1）进行测序和缺失重复分析。
回顾性分析和前瞻性研究共确定了 135 名在我们诊所就诊评估杂合子 FH 的成年先证者。29 名个体（21%）携带有致病性或可能致病性的单基因变异。在进行基因检测之前，使用 DLCN 标准，35 名（26%）个体符合 FH 明确诊断的标准。使用 Simon Broome 标准，有 30 名（22%）患者符合标准，使用美国 MEDPED 标准，有 29 名（21%）患者符合标准。根据标准，基因检测可额外诊断出 11-14 名 FH 患者。
与仅基于临床标准的分类相比，基因检测可诊断出近 50%的 FH 患者。
