Prevalence of Mutations in Mendelian Stroke Genes in Early Onset Stroke Patients.

Autor: Park HK; Department of Neurology, Inje University Ilsan Paik Hospital, Inje University College of Medicine, Goyang, South Korea., Lee KJ; Department of Neurology, Cerebrovascular Center, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea.; Department of Neurology, Korea University Guro Hospital, Seoul, South Korea., Park JM; Department of Neurology, Uijeongbu Eulji Medical Center, Eulji University, Uijeongbu, South Korea., Kang K; Department of Neurology, Nowon Eulji Medical Center, Eulji University, Seoul, South Korea., Lee SJ; Department of Neurology, Eulji University Hospital, Eulji University, Daejeon, South Korea., Kim JG; Department of Neurology, Eulji University Hospital, Eulji University, Daejeon, South Korea., Cha JK; Department of Neurology, Dong-A University Hospital, Busan, South Korea., Kim DH; Department of Neurology, Dong-A University Hospital, Busan, South Korea., Han MK; Department of Neurology, Cerebrovascular Center, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea., Kang J; Department of Neurology, Cerebrovascular Center, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea., Kim BJ; Department of Neurology, Cerebrovascular Center, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea., Park TH; Department of Neurology, Seoul Medical Center, Seoul, South Korea., Park MS; Department of Neurology, Seoul Hospital, Ewha Woman's University College of Medicine, Seoul, South Korea., Lee KB; Department of Neurology, Soonchunhyang University Hospital, Seoul, South Korea., Lee J; Department of Neurology, Yeungnam University Hospital, Daegu, South Korea., Hong KS; Department of Neurology, Inje University Ilsan Paik Hospital, Inje University College of Medicine, Goyang, South Korea., Cho YJ; Department of Neurology, Inje University Ilsan Paik Hospital, Inje University College of Medicine, Goyang, South Korea., Lee BC; Department of Neurology, Hallym University Sacred Heart Hospital, Anyang, South Korea., Yu KH; Department of Neurology, Hallym University Sacred Heart Hospital, Anyang, South Korea., Oh MS; Department of Neurology, Hallym University Sacred Heart Hospital, Anyang, South Korea., Kim JT; Department of Neurology, Chonnam National University Hospital, Gwangju, South Korea., Choi KH; Department of Neurology, Chonnam National University Hospital, Gwangju, South Korea., Kim DE; Department of Neurology, Dongguk University Ilsan Hospital, Goyang, South Korea., Ryu WS; Department of Neurology, Dongguk University Ilsan Hospital, Goyang, South Korea.; Research Center for Artificial Intelligence, JLK Corporation, Seoul, South Korea., Choi JC; Department of Neurology, Jeju National University Hospital, Jeju National University School of Medicine, Jeju, South Korea., Kwon JH; Department of Neurology, Ulsan University College of Medicine, Ulsan, South Korea., Kim WJ; Department of Neurology, Ulsan University College of Medicine, Ulsan, South Korea., Shin DI; Department of Neurology, Chungbuk University Hospital, Cheongju, South Korea., Sohn SI; Department of Neurology, Keimyung University Dongsan Medical Center, Daegu, South Korea., Hong JH; Department of Neurology, Keimyung University Dongsan Medical Center, Daegu, South Korea., Lee J; Department of Biostatistics, Korea University College of Medicine, Seoul, South Korea., Lee K; Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea., Song J; Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea., Bae JS; Research Institute of Future Medicine, Samsung Medical Center, Seoul, South Korea., Cheong HS; Research Institute for Life Science, GW Vitek, Seoul, South Korea., Debette S; University of Bordeaux, Bordeaux Population Health Research Center, Bordeaux, France., Bae HJ; Department of Neurology, Cerebrovascular Center, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea.
Jazyk: angličtina
Zdroj: Annals of neurology [Ann Neurol] 2023 Apr; Vol. 93 (4), pp. 768-782. Date of Electronic Publication: 2023 Jan 16.
DOI: 10.1002/ana.26575
Abstrakt: Objective: Heritability of stroke is assumed not to be low, especially in the young stroke population. However, most genetic studies have been performed in highly selected patients with typical clinical or neuroimaging characteristics. We investigated the prevalence of 15 Mendelian stroke genes and explored the relationships between variants and the clinical and neuroimaging characteristics in a large, unselected, young stroke population.
Methods: We enrolled patients aged ≤55 years with stroke or transient ischemic attack from a prospective, nationwide, multicenter stroke registry. We identified clinically relevant genetic variants (CRGVs) in 15 Mendelian stroke genes (GLA, NOTCH3, HTRA1, RNF213, ACVRL1, ENG, CBS, TREX1, ABCC6, COL4A1, FBN1, NF1, COL3A1, MT-TL1, and APP) using a customized, targeted next generation sequencing panel.
Results: Among 1,033 patients, 131 (12.7%) had 28 CRGVs, most frequently in RNF213 (n = 59), followed by ABCC6 (n = 53) and NOTCH3 (n = 15). The frequency of CRGVs differed by ischemic stroke subtypes (p < 0.01): the highest in other determined etiology (20.1%), followed by large artery atherosclerosis (13.6%). It also differed between patients aged ≤35 years and those aged 51 to 55 years (17.1% vs 9.3%, p = 0.02). Only 27.1% and 26.7% of patients with RNF213 and NOTCH3 variants had typical neuroimaging features of the corresponding disorders, respectively. Variants of uncertain significance (VUSs) were found in 15.4% patients.
Interpretation: CRGVs in 15 Mendelian stroke genes may not be uncommon in the young stroke population. The majority of patients with CRGVs did not have typical features of the corresponding monogenic disorders. Clinical implications of having CRGVs or VUSs should be explored. ANN NEUROL 2023;93:768-782.
(© 2022 American Neurological Association.)
Databáze: MEDLINE
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