Noda Kotaro, Hattori Yorito, Hori Mika, Harada-Shiba Mariko, Ihara Masafumi
From the Department of Neurology (K.N., Y.H., M.I.), National Cerebral and Cardiovascular Center, Suita; Department of Neurology and Neurological Science (K.N.), Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University; Department of Endocrinology (M.H.), Research Institute of Environmental Medicine, Nagoya University; and Cardiovascular Center (M.H.-S.), Osaka Medical and Pharmaceutical University, Takatsuki, Japan.
Neurol Genet. 2023 Sep 5;9(5):e200099. doi: 10.1212/NXG.0000000000200099. eCollection 2023 Oct.
Familial hypercholesterolemia (FH), caused by p.E32K, is characterized by early-onset coronary artery disease. However, the relationship between p.E32K and cerebrovascular disease is unclear. One of our patients with the p.E32K had several intracranial artery stenoses (ICAS). The objective of this case series was to identify factors that may be associated with ICAS in the variant carriers.
A 75-year-old Japanese woman with FH carrying p.E32K was found to have 5 asymptomatic ICAS when brain magnetic resonance angiography (MRA) was performed. We retrospectively investigated additional patients with FH who underwent brain MRA at our institution to explore the unknown factors accelerating ICAS.
We investigated an additional 5 patients with FH who underwent brain MRA. Of them, only one had mild ICAS. The p.R4810K that is an established genetic risk for ICAS, particularly in East Asians, was identified only in the patient with 5 ICAS.
PCSK9 and RNF213 play an important role in lipid metabolism and endothelial integrity. Therefore, together, these variants could be involved in the development of multiple ICAS. Our case series indicated that p.E32K carriers should undergo early brain screening to obtain appropriate stroke prevention measures in the asymptomatic stage.
由p.E32K引起的家族性高胆固醇血症（FH）的特征是早发性冠状动脉疾病。然而，p.E32K与脑血管疾病之间的关系尚不清楚。我们的一名携带p.E32K的患者有多处颅内动脉狭窄（ICAS）。本病例系列的目的是确定可能与该变异携带者ICAS相关的因素。
一名携带p.E32K的75岁日本FH女性在进行脑磁共振血管造影（MRA）时被发现有5处无症状ICAS。我们回顾性研究了在我们机构接受脑MRA检查的其他FH患者，以探索加速ICAS的未知因素。
我们研究了另外5名接受脑MRA检查的FH患者。其中，只有一人有轻度ICAS。仅在有5处ICAS的患者中发现了p.R4810K，这是ICAS的一种已确定的遗传风险，特别是在东亚人群中。
PCSK9和RNF213在脂质代谢和内皮完整性中起重要作用。因此，这些变异可能共同参与了多处ICAS的发生发展。我们的病例系列表明，p.E32K携带者应在无症状阶段接受早期脑部筛查，以采取适当的中风预防措施。
