Curr Opin Lipidol. 2018 Apr;29(2):65-71. doi: 10.1097/MOL.0000000000000496.
We provide an overview of molecular diagnosis for familial hypercholesterolemia in France including descriptions of the mutational spectrum, polygenic susceptibility and perspectives for improvement in familial hypercholesterolemia diagnosis.
Molecular testing for familial hypercholesterolemia is recommended for patients with a LDL-cholesterol level above 190 mg/dl (adults) associated with criteria related to personal and family history of hypercholesterolemia and premature cardiovascular disease. Among the 3381 index cases included with these characteristics in the French registry for familial hypercholesterolemia, 2054 underwent molecular diagnosis and 1150 (56%) were found to have mutations (93.5% in LDL Receptor (LDLR), 4.7% in apolipoprotein B and 1.8% in Proprotein convertase subtilisin/kexin type 9). A total of 416 different pathogenic variants were found in the LDLR gene. Based on gene score calculation, a polygenic origin may be suggested in 36% of nonmutated patients. Involvement of genetic counselors and education of healthcare professionals for genetics of familial hypercholesterolemia are underway with the aim of improving the efficiency of the diagnosis.
Genetic cascade screening for familial hypercholesterolemia is currently implemented in France with the complexity to address the diversity of its molecular cause in index cases. Optimization of patient care pathways is critical to improve both the rate of diagnosis and the management of familial hypercholesterolemia patients.
本文概述了法国家族性高胆固醇血症的分子诊断，包括突变谱、多基因易感性的描述以及提高家族性高胆固醇血症诊断的前景。
对于 LDL-胆固醇水平高于 190mg/dl（成人）且伴有个人和家族高胆固醇血症及早发心血管疾病史相关标准的家族性高胆固醇血症患者，建议进行分子检测。在法国家族性高胆固醇血症登记处的这些特征的 3381 例索引病例中，有 2054 例接受了分子诊断，发现 1150 例（56%）有突变（93.5%在 LDL 受体（LDLR），4.7%在载脂蛋白 B，1.8%在脯氨酸内切酶/肠激酶 9）。在 LDLR 基因中发现了 416 种不同的致病性变异。根据基因评分计算，36%的非突变患者可能存在多基因起源。正在进行遗传咨询师的参与和家族性高胆固醇血症遗传学的医疗保健专业人员的教育，目的是提高诊断效率。
目前法国正在对家族性高胆固醇血症进行遗传级联筛查，需要解决索引病例中分子病因的多样性。优化患者护理途径对于提高家族性高胆固醇血症的诊断率和患者管理至关重要。
