Kullo Iftikhar J, Bailey Kent R
Department of Cardiovascular Diseases and the Gonda Vascular Center, Mayo Clinic, Rochester, MN 55902, USA.
Department of Health Sciences Research (KRB), Mayo Clinic, Rochester, MN 55902, USA.
J Pers Med. 2018 Aug 23;8(3):27. doi: 10.3390/jpm8030027.
To inform guidelines for screening family members of patients with familial hypercholesterolemia (FH), we designed a clinical trial to compare the yield of cascade screening in FH patients with and without an identifiable pathogenic variant. Participants with hypercholesterolemia (Low-density lipoprotein cholesterol (LDL-C) > 155 mg/dL) underwent sequencing of , , and and genotyping of six single nucleotide polymorphisms associated with LDL-C followed by calculation of a polygenic score for LDL-C. We identified 24 patients with definite FH (pathogenic variant in one of the three FH genes), 76 patients with probable FH (Dutch lipid clinic network (DLCN) score ≥ 6, no pathogenic variant), and 262 patients with possible FH (DLCN score 3⁻5, no pathogenic variant). We will enroll 50 patients with definite FH by recruiting an additional 26 from the FH Clinic at Mayo and 50 patients each with probable and possible FH, matching on age and sex. Family members of patients with definite FH will undergo testing for the relevant pathogenic variant using saliva kits and family members of those with probable/possible FH will have a lipid profile checked. We will assess the number of new cases detected (defined as presence of a pathogenic variant in the family member of definite FH patient or LDL-C > 155 mg/dL (>130 mg/dL in children) in family members of probable/possible FH patients, and the cost of detecting a new case. The proposed clinical trial will compare the yield and cost of cascade screening for FH patients with/without an identifiable pathogenic variant, and thereby inform guidelines for cascade screening for FH.
为制定家族性高胆固醇血症（FH）患者家庭成员筛查指南，我们设计了一项临床试验，以比较在有和没有可识别致病变异的FH患者中进行级联筛查的检出率。高胆固醇血症患者（低密度脂蛋白胆固醇（LDL-C）>155mg/dL）接受了 、 和 的测序以及与LDL-C相关的六个单核苷酸多态性的基因分型，随后计算LDL-C的多基因评分。我们确定了24例确诊FH患者（三个FH基因之一存在致病变异）、76例可能FH患者（荷兰脂质诊所网络（DLCN）评分≥6，无致病变异）和262例可能FH患者（DLCN评分为3-5，无致病变异）。我们将通过从梅奥诊所的FH门诊额外招募26例患者来纳入50例确诊FH患者，以及各50例可能和可能FH患者，并根据年龄和性别进行匹配。确诊FH患者的家庭成员将使用唾液试剂盒进行相关致病变异检测，可能/可能FH患者的家庭成员将进行血脂检查。我们将评估检测到的新病例数（定义为确诊FH患者家庭成员中存在致病变异，或可能/可能FH患者家庭成员中LDL-C>155mg/dL（儿童>130mg/dL））以及检测一例新病例的成本。拟议的临床试验将比较有/无可识别致病变异的FH患者级联筛查的检出率和成本，从而为FH级联筛查指南提供依据。
