Sen Suo, Cheng Fang, Wenting Liu, Qingan Liu, Zhuobo Zhang, Junlei Chang, Guozhong Li
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引用次数: 0
Abstract
Unilateral moyamoya disease (MMD) represents a distinct subtype characterised by occlusive changes in the circle of Willis and abnormal vascular network formation. However, the aetiology and pathogenesis of unilateral MMD remain unclear. In this study, genetic screening of a family with unilateral MMD using whole-genome sequencing helped identify the c.1205 C > A variant of FOXM1, which encodes the transcription factor FOXM1 and plays a crucial role in angiogenesis and cell proliferation, as a susceptibility gene mutation. We demonstrated that this mutation significantly attenuated the proangiogenic effects of FOXM1 in human brain endothelial cells, leading to reduced proliferation, migration, and tube formation. Furthermore, FOXM1 c.1205 C > A results in increased apoptosis of human brain endothelial cells, mediated by the downregulation of the transcription of the apoptosis-inhibiting protein BCL2. These results suggest a potential role for the FOXM1 c.1205 C > A mutation in the pathogenesis of unilateral MMD and may contribute to the understanding and treatment of this condition.
单侧莫亚莫亚病（MMD）是一种独特的亚型疾病，其特点是威利斯圈发生闭塞性改变和血管网形成异常。然而，单侧莫亚莫亚病的病因和发病机制仍不清楚。在这项研究中，通过全基因组测序对一个单侧 MMD 家族进行基因筛查，发现了 FOXM1 的 c.1205 C > A 变异，该基因编码转录因子 FOXM1，在血管生成和细胞增殖中起着至关重要的作用。我们证实，这种突变显著削弱了 FOXM1 在人脑内皮细胞中的促血管生成作用，导致增殖、迁移和管形成减少。此外，FOXM1 c.1205 C > A 会导致人脑内皮细胞凋亡增加，而凋亡抑制蛋白 BCL2 的转录被下调。这些结果表明，FOXM1 c.1205 C > A 突变在单侧 MMD 的发病机制中具有潜在的作用，可能有助于对这种疾病的理解和治疗。
期刊介绍：
Human Genetics is a monthly journal publishing original and timely articles on all aspects of human genetics. The Journal particularly welcomes articles in the areas of Behavioral genetics, Bioinformatics, Cancer genetics and genomics, Cytogenetics, Developmental genetics, Disease association studies, Dysmorphology, ELSI (ethical, legal and social issues), Evolutionary genetics, Gene expression, Gene structure and organization, Genetics of complex diseases and epistatic interactions, Genetic epidemiology, Genome biology, Genome structure and organization, Genotype-phenotype relationships, Human Genomics, Immunogenetics and genomics, Linkage analysis and genetic mapping, Methods in Statistical Genetics, Molecular diagnostics, Mutation detection and analysis, Neurogenetics, Physical mapping and Population Genetics. Articles reporting animal models relevant to human biology or disease are also welcome. Preference will be given to those articles which address clinically relevant questions or which provide new insights into human biology.
Unless reporting entirely novel and unusual aspects of a topic, clinical case reports, cytogenetic case reports, papers on descriptive population genetics, articles dealing with the frequency of polymorphisms or additional mutations within genes in which numerous lesions have already been described, and papers that report meta-analyses of previously published datasets will normally not be accepted.
The Journal typically will not consider for publication manuscripts that report merely the isolation, map position, structure, and tissue expression profile of a gene of unknown function unless the gene is of particular interest or is a candidate gene involved in a human trait or disorder.
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