期刊
STROKE
卷 51, 期 10, 页码 3007-3017出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/STROKEAHA.120.029517
关键词
cerebral small vessel diseases; genes; guideline; phenotype; systematic review
资金
- Health Data Research UK (Medical Research Councilfunded) fellowship [MR/S004130/1]
- Medical Research Council Clinical Research Training Fellowship [MR/P001823/1]
- MRC [MR/S004130/1] Funding Source: UKRI
Background and Purpose: An important minority of cerebral small vessel disease (cSVD) is monogenic. Many monogenic cSVD genes are recognized to be associated with extracerebral phenotypes. We assessed the frequency of these phenotypes in existing literature. Methods: We performed a systematic review following the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), searching Medline/Embase for publications describing individuals with pathogenic variants inCOL4A1/2,TREX1,HTRA1,ADA2, andCTSAgenes (PROSPERO 74804). We included any publication reporting on >= 1 individual with a pathogenic variant and their clinically relevant phenotype. We extracted individuals' characteristics and information about associated extracerebral phenotypes and stroke/transient ischemic attack. We noted any novel extracerebral phenotypes and looked for shared phenotypes between monogenic cSVDs. Results: After screening 6048 publications, we included 96COL4A1(350 individuals), 32TREX1(115 individuals), 43HTRA1(38 homozygous/61 heterozygous individuals), 16COL4A2(37 individuals), 119ADA2(209 individuals), and 3CTSA(14 individuals) publications. The majority of individuals originated from Europe/North America, except forHTRA1, where most were from Asia. Age varied widely,ADA2individuals being youngest and heterozygousHTRA1/CTSAindividuals oldest. Sex distribution appeared equal. Extracerebral phenotypes were common: 14% to 100% of individuals with a pathogenic variant manifested at least one extracerebral phenotype (14%COL4A2, 43%HTRA1heterozygotes, 47%COL4A1, 57%TREX1, 91%ADA2, 94%HTRA1homozygotes, and 100%CTSAindividuals). Indeed, for 4 of 7 genes, an extracerebral phenotype was observed more frequently than stroke/transient ischemic attack. Ocular, renal, hepatic, muscle, and hematologic systems were each involved in more than one monogenic cSVD. Conclusions: Extracerebral phenotypes are common in monogenic cSVD with extracerebral system involvement shared between genes. However, inherent biases in the existing literature mean that further data from large-scale population-based longitudinal studies collecting health outcomes in a systematic unbiased way is warranted. The emerging knowledge will help to select patients for testing, inform clinical management, and provide further insights into the underlying mechanisms of cSVD.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据