Blokhina Anastasia V, Ershova Alexandra I, Meshkov Alexey N, Kiseleva Anna V, Klimushina Marina V, Zharikova Anastasia A, Sotnikova Evgeniia A, Ramensky Vasily E, Drapkina Oxana M
Laboratory of Clinomics, National Medical Research Center for Therapy and Preventive Medicine of the Ministry of Healthcare of the Russian Federation, Moscow, Russia.
Laboratory of Molecular Genetics, National Medical Research Center for Therapy and Preventive Medicine of the Ministry of Healthcare of the Russian Federation, Moscow, Russia.
Front Cardiovasc Med. 2022 Aug 25;9:982607. doi: 10.3389/fcvm.2022.982607. eCollection 2022.
One of the most common autosomal dominant disorders is familial hypercholesterolemia (FH), causing premature atherosclerotic cardiovascular diseases and a high risk of death due to lifelong exposure to elevated low-density lipoprotein cholesterol (LDL-C) levels. FH has a proven arsenal of treatments and the opportunity for genetic diagnosis. Despite this, FH remains largely underdiagnosed worldwide. Cascade screening is a cost-effective method for the identification of new patients with FH and the prevention of cardiovascular diseases. It is usually based only on clinical data. We describe a 48-year-old index patient with a very high LDL-C level without controlled guidelines-based medication, premature atherosclerosis, and a rare variant in the low-density lipoprotein receptor () gene. Phenotypic cascade screening identified three additional FH relatives, namely the proband's daughter, and two young grandsons. The genetic screening made it possible to rule out FH in the proband's younger grandson. This clinical case demonstrates that genetic cascade screening is the most effective way of identifying new FH cases. We also first described in detail the phenotype of patients with a likely pathogenic variant -p.K223_D227dup.
最常见的常染色体显性疾病之一是家族性高胆固醇血症（FH），它会导致过早发生动脉粥样硬化性心血管疾病，并且由于终生暴露于升高的低密度脂蛋白胆固醇（LDL-C）水平而具有较高的死亡风险。FH有一系列经过验证的治疗方法以及进行基因诊断的机会。尽管如此，FH在全球范围内仍大多未得到诊断。级联筛查是识别新的FH患者和预防心血管疾病的一种具有成本效益的方法。它通常仅基于临床数据。我们描述了一名48岁的索引患者，其低密度脂蛋白胆固醇水平非常高，未遵循基于指南的药物治疗，存在过早动脉粥样硬化，并且低密度脂蛋白受体（）基因中有一个罕见变异。表型级联筛查又识别出另外三名FH亲属，即先证者的女儿和两个年幼的孙子。基因筛查排除了先证者年幼孙子患FH的可能性。这个临床病例表明，基因级联筛查是识别新的FH病例的最有效方法。我们还首次详细描述了具有可能致病变异-p.K223_D227dup的患者的表型。
