The genetics and screening of familial hypercholesterolaemia.
The genetics and screening of familial hypercholesterolaemia.
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DOI：
10.1186/s12929-016-0256-1
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发表时间：
2016-04-16
影响因子：
11
通讯作者：
Watterson S
中科院分区：
文献类型：
--
作者：
Henderson R;O'Kane M;McGilligan V;Watterson S
家族性高胆固醇血症是一种常染色体显性遗传疾病，可导致血液胆固醇升高和动脉粥样硬化风险显著增加。它被认为是一种罕见的疾病。然而，它影响全球250人中的1人，使其成为重要的公共卫生问题。在具有奠基者效应的社区，观察到较高的疾病流行率。我们讨论了家族性高胆固醇血症的遗传基础，研究了已知与LDLR、ApoB、PCSK 9和LDLRAP 1基因外显子之间的疾病相关的变异体的分布。我们还讨论了家族性高胆固醇血症的筛查计划及其成本效益。诊断通常使用荷兰脂质诊所网络（DCLN），西蒙布鲁姆登记（SBR）或早期诊断以防止早期死亡（MEDPED）标准之一进行，其中每一个都需要不同的患者数据集。新病例可以通过筛查索引病例的家庭成员来确定，索引病例是在称为级联筛查的过程中转诊到脂质诊所而确定的。或者，可以使用普遍筛查，从而对群体进行系统筛查。目前，通过级联筛查识别家族性高胆固醇血症病例比普遍筛查更具成本效益。然而，近年来患者DNA测序的成本已经大幅下降，如果进展速度继续下去，这种情况可能会改变。
Familial Hypercholesterolaemia is an autosomal, dominant genetic disorder that leads to elevated blood cholesterol and a dramatically increased risk of atherosclerosis. It is perceived as a rare condition. However it affects 1 in 250 of the population globally, making it an important public health concern. In communities with founder effects, higher disease prevalences are observed. We discuss the genetic basis of familial hypercholesterolaemia, examining the distribution of variants known to be associated with the condition across the exons of the genes LDLR, ApoB, PCSK9 and LDLRAP1. We also discuss screening programmes for familial hypercholesterolaemia and their cost-effectiveness. Diagnosis typically occurs using one of the Dutch Lipid Clinic Network (DCLN), Simon Broome Register (SBR) or Make Early Diagnosis to Prevent Early Death (MEDPED) criteria, each of which requires a different set of patient data. New cases can be identified by screening the family members of an index case that has been identified as a result of referral to a lipid clinic in a process called cascade screening. Alternatively, universal screening may be used whereby a population is systematically screened. It is currently significantly more cost effective to identify familial hypercholesterolaemia cases through cascade screening than universal screening. However, the cost of sequencing patient DNA has fallen dramatically in recent years and if the rate of progress continues, this may change.