Ajufo Ezimamaka, deGoma Emil M, Raper Anna, Yu Kristen Dilzell, Cuchel Marina, Rader Daniel J
Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Department of Internal Medicine, University of Texas Southwestern, Dallas, TX, USA.
Genet Med. 2021 Sep;23(9):1697-1704. doi: 10.1038/s41436-021-01192-z. Epub 2021 May 26.
Family-based cascade screening from index probands is considered an effective way of identifying undiagnosed individuals with familial hypercholesterolemia (FH). The role of genetic testing of the proband in the success of cascade screening for FH is unknown.
We randomized 240 individuals with a clinical diagnosis of FH to genetic testing for FH (n = 160) or usual care with lipid testing alone (n = 80). The primary study endpoint was the proportion of probands with at least one relative enrolled in the study within one year after the notification of results.
Proband median age was 59 (47-67) and 71% were female. Only 28 (12%) probands succeeded in enrolling a relative. While the genetic testing group had a higher proportion of probands with relatives enrolled (13.1%) compared with the usual care group (8.8%), this difference was not significant (p = 0.40). In subgroup analyses, enrollment of a relative was higher in the pathogenic variant group (22.7%) compared to the no pathogenic variant (9.5%) and usual care groups (8.8%) (p = 0.04).
We observed a low rate of family participation in cascade screening despite repeated recommendations to probands. Compared to usual care, genetic testing did not improve family participation in cascade screening for FH.
NCT04526457.
从索引先证者进行基于家庭的级联筛查被认为是识别未确诊的家族性高胆固醇血症（FH）患者的有效方法。先证者基因检测在FH级联筛查成功中的作用尚不清楚。
我们将240例临床诊断为FH的个体随机分为FH基因检测组（n = 160）或仅进行血脂检测的常规治疗组（n = 80）。主要研究终点是在结果通知后一年内至少有一名亲属参与研究的先证者比例。
先证者的中位年龄为59岁（47 - 67岁），71%为女性。只有28名（12%）先证者成功招募到一名亲属。虽然基因检测组中招募到亲属的先证者比例（13.1%）高于常规治疗组（8.8%），但差异不显著（p = 0.40）。在亚组分析中，与无致病变异组（9.5%）和常规治疗组（8.8%）相比，致病变异组中亲属的参与率更高（22.7%）（p = 0.04）。
尽管反复向先证者提出建议，但我们观察到家庭参与级联筛查的比例较低。与常规治疗相比，基因检测并未提高家庭参与FH级联筛查的比例。
NCT04526457。
