{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:33:53Z","timestamp":1760060033279,"version":"build-2065373602"},"reference-count":107,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,26]],"date-time":"2025-07-26T00:00:00Z","timestamp":1753488000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives\uff1a Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a prevalent Mendelian disorder caused by mutations in the NOTCH3 gene, primarily impacting cerebral small blood vessels. This review aims to explore the involvement of large intracranial arteries in CADASIL, particularly focusing on the association with RNF213 polymorphisms, especially in Asian populations. Methods\uff1a A comprehensive literature review was conducted to gather data on the morphological features of both small and large intracranial arteries in CADASIL, examining clinical manifestations, imaging findings, and genetic associations. Results\uff1a The findings indicate that while CADASIL is predominantly characterized by small vessel disease, a significant number of patients also exhibit large artery involvement, particularly Asian populations where RNF213 polymorphisms may play a critical role. The review highlights the evidence of intracranial stenosis and the potential implications of traditional vascular risk factors, such as hypertension and diabetes mellitus, which are prevalent in these populations. Conclusions\uff1a The involvement of larger intracranial arteries in CADASIL underscores the complexity of the disease, suggesting that both genetic predispositions and environmental factors contribute to vascular abnormalities. Further research is needed to clarify these relationships and improve diagnostic and therapeutic strategies for CADASIL patients.<\/jats:p>","DOI":"10.3390\/genes16080882","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T14:50:03Z","timestamp":1753714203000},"page":"882","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intracranial Large Artery Involvement in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy: A Tale of Two Genes?"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7530-818X","authenticated-orcid":false,"given":"Marialuisa","family":"Zedde","sequence":"first","affiliation":[{"name":"Neurology Unit, Stroke Unit, Azienda Unit\u00e0 Sanitaria Locale-IRCCS di Reggio Emilia, Viale Risorgimento 80, 42123 Reggio Emilia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0512-9298","authenticated-orcid":false,"given":"Rosario","family":"Pascarella","sequence":"additional","affiliation":[{"name":"Neuroradiology Unit, Ospedale Santa Maria della Misericordia, AULSS 5 Polesana, 45100 Rovigo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.5853\/jos.2015.17.1.7","article-title":"Genetics of cerebral small vessel disease","volume":"17","author":"Choi","year":"2015","journal-title":"J. Stroke"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3988\/jcn.2010.6.1.1","article-title":"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: A genetic cause of cerebral small vessel disease","volume":"6","author":"Choi","year":"2010","journal-title":"J. Clin. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/S1474-4422(09)70127-9","article-title":"Cadasil","volume":"8","author":"Chabriat","year":"2009","journal-title":"Lancet Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1093\/brain\/awn364","article-title":"Congruence between NOTCH3 mutations and GOM in 131 CADASIL patients","volume":"132","author":"Tikka","year":"2009","journal-title":"Brain"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1038\/383707a0","article-title":"Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia","volume":"383","author":"Joutel","year":"1996","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s00401-006-0116-2","article-title":"Notch3 ectodomain is a major component of granular osmiophilic material (GOM) in CADASIL","volume":"112","author":"Ishiko","year":"2006","journal-title":"Acta Neuropathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/jcbfm.2015.62","article-title":"Perturbations of the cerebrovascular matrisome: A convergent mechanism in small vessel disease of the brain?","volume":"36","author":"Joutel","year":"2016","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1136\/jnnp.2004.051847","article-title":"The prevalence of cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) in the west of Scotland","volume":"76","author":"Razvi","year":"2005","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1007\/s00415-014-7533-2","article-title":"CADASIL in central Italy: A retrospective clinical and genetic study in 229 patients","volume":"262","author":"Bianchi","year":"2015","journal-title":"J. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1111\/ane.12266","article-title":"Changing clinical patterns and increasing prevalence in CADASIL","volume":"130","author":"Moreton","year":"2014","journal-title":"Acta Neurol. Scand."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1212\/WNL.0b013e31824d586c","article-title":"The minimum prevalence of CADASIL in northeast England","volume":"78","author":"Narayan","year":"2012","journal-title":"Neurology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1002\/acn3.344","article-title":"Archetypal NOTCH3 mutations frequent in public exome: Implications for CADASIL","volume":"3","author":"Rutten","year":"2016","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1161\/STROKEAHA.119.028840","article-title":"Global assessment of Mendelian stroke genetic prevalence in 101 635 individuals from 7 ethnic groups","volume":"51","author":"Grami","year":"2020","journal-title":"Stroke"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.1212\/01.wnl.0000246601.70918.06","article-title":"Intracerebral hemorrhages in CADASIL","volume":"67","author":"Choi","year":"2006","journal-title":"Neurology"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Liao, Y.-C., Hsiao, C.-T., Fuh, J.-L., Chern, C.-M., Lee, W.-J., Guo, Y.-C., Wang, S.-J., Lee, I.-H., Liu, Y.-T., and Wang, Y.-F. (2015). Characterization of CADASIL among the Han Chinese in Taiwan: Distinct genotypic and phenotypic profiles. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0136501"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1002\/ana.410440506","article-title":"The phenotypic spectrum of CADASIL: Clinical findings in 102 cases","volume":"44","author":"Dichgans","year":"1998","journal-title":"Ann. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1161\/01.STR.0000257968.24015.bf","article-title":"Lacunar infarcts are the main correlate with cognitive dysfunction in CADASIL","volume":"38","author":"Liem","year":"2007","journal-title":"Stroke"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1212\/WNL.56.5.628","article-title":"MRI hyperintensities of the temporal lobe and external capsule in patients with CADASIL","volume":"56","author":"Jarosz","year":"2001","journal-title":"Neurology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1161\/STROKEAHA.115.010696","article-title":"Predictors of clinical worsening in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: Prospective cohort study","volume":"47","author":"Chabriat","year":"2016","journal-title":"Stroke"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1161\/STROKEAHA.114.005604","article-title":"Biomarker panels in ischemic stroke","volume":"46","author":"Jickling","year":"2015","journal-title":"Stroke"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/jcbfm.2015.68","article-title":"Blood and CSF biomarkers in brain subcortical ischemic vascular disease: Involved pathways and clinical applicability","volume":"36","author":"Bustamante","year":"2016","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1161\/01.STR.24.1.122","article-title":"Autosomal dominant leukoencephalopathy and subcortical ischemic stroke. A clinicopathological study","volume":"24","author":"Baudrimont","year":"1993","journal-title":"Stroke"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1007\/BF00571504","article-title":"Systemic vascular smooth muscle cell impairment in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy","volume":"89","author":"Ruchoux","year":"1995","journal-title":"Acta Neuropathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/S0002-9440(10)63824-2","article-title":"Transgenic mice expressing mutant Notch3 develop vascular alterations characteristic of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy","volume":"162","author":"Ruchoux","year":"2003","journal-title":"Am. J. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.jstrokecerebrovasdis.2011.07.002","article-title":"Diversity of stroke presentation in CADASIL: Study from patients harboring the predominant NOTCH3 mutation R544C","volume":"22","author":"Choi","year":"2013","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.jns.2015.11.029","article-title":"Intracranial arterial disease in CADASIL patients","volume":"359","author":"Kang","year":"2015","journal-title":"J. Neurol. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"ATMP103","DOI":"10.1161\/str.50.suppl_1.TMP103","article-title":"Relationship between parent brain large arteries and their penetrating arterial offspring","volume":"50","author":"Gutierrez","year":"2019","journal-title":"Stroke"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e166134","DOI":"10.1172\/JCI166134","article-title":"Age-related loss of Notch3 underlies brain vascular contractility deficiencies, glymphatic dysfunction, and neurodegeneration in mice","volume":"134","author":"Romay","year":"2024","journal-title":"J. Clin. Investig."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/s10038-018-0428-9","article-title":"RNF213-related susceptibility of Japanese CADASIL patients to intracranial arterial stenosis","volume":"63","author":"Yeung","year":"2018","journal-title":"J. Hum. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Zedde, M., Grisendi, I., Assenza, F., Napoli, M., Moratti, C., Pavone, C., Bonacini, L., Di Cecco, G., D\u2019aniello, S., and Stoenoiu, M.S. (2024). RNF213 Polymorphisms in Intracranial Artery Dissection. Genes, 15.","DOI":"10.3390\/genes15060725"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e017660","DOI":"10.1161\/JAHA.120.017660","article-title":"Role of the RNF213 Variant in Vascular Outcomes in Patients With Intracranial Atherosclerosis","volume":"10","author":"Kim","year":"2021","journal-title":"J. Am. Heart Assoc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1111\/j.1750-3639.2002.tb00451.x","article-title":"CADASIL: A common form of hereditary arteriopathy causing brain infarcts and dementia","volume":"12","author":"Kalimo","year":"2002","journal-title":"Brain Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/S0140-6736(95)91557-5","article-title":"Clinical spectrum of CADASIL: A study of 7 families. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy","volume":"346","author":"Chabriat","year":"1995","journal-title":"Lancet"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1212\/WNL.51.2.452","article-title":"Patterns of MRI lesions in CADASIL","volume":"51","author":"Chabriat","year":"1998","journal-title":"Neurology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2637","DOI":"10.1161\/01.STR.30.12.2637","article-title":"Clinical severity in CADASIL related to ultrastructural damage in white matter: In vivo study with diffusion tensor MRI","volume":"30","author":"Chabriat","year":"1999","journal-title":"Stroke"},{"key":"ref_36","first-page":"2115","article-title":"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: MR findings","volume":"16","author":"Skehan","year":"1995","journal-title":"Am. J. Neuroradiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1007\/BF00386260","article-title":"Small arterial granular degeneration in familial Binswanger\u2019s syndrome","volume":"87","author":"Amer","year":"1994","journal-title":"Acta Neuropathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/BF00691704","article-title":"Hereditary multi-infarct dementia. Morphological and clinical studies of a new disease","volume":"39","author":"Sourander","year":"1977","journal-title":"Acta Neuropathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s00401-002-0530-z","article-title":"Morphometric analysis of ultrastructural vascular changes in CADASIL: Analysis of 50 skin biopsy specimens and pathogenic implications","volume":"104","author":"Brulin","year":"2002","journal-title":"Acta Neuropathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1111\/j.1750-3639.2004.tb00078.x","article-title":"Fibrosis and stenosis of the long penetrating cerebral arteries: The cause of the white matter pathology in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy","volume":"14","author":"Miao","year":"2004","journal-title":"Brain Pathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1161\/01.STR.22.4.442","article-title":"Medullary arteries in aging and dementia","volume":"22","author":"Furuta","year":"1991","journal-title":"Stroke"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2222","DOI":"10.1161\/01.STR.28.11.2222","article-title":"Nonhypertensive cerebral small-vessel disease. An autopsy study","volume":"28","author":"Lammie","year":"1997","journal-title":"Stroke"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2565","DOI":"10.1161\/01.STR.0000032620.91848.1C","article-title":"Arterial changes in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in relation to pathogenesis of diffuse myelin loss of cerebral white matter: Examination of cerebral medullary arteries by reconstruction of serial sections of an autopsy case","volume":"33","author":"Okeda","year":"2002","journal-title":"Stroke"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1161\/01.STR.14.6.924","article-title":"Cerebral amyloid angiopathy: Incidence and complications in the aging brain. II. The distribution of amyloid vascular changes","volume":"14","author":"Vinters","year":"1983","journal-title":"Stroke"},{"key":"ref_45","first-page":"1268","article-title":"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: Decrease in regional cerebral blood volume in hyperintense subcortical lesions inversely correlates with disability and cognitive performance","volume":"22","author":"Bruening","year":"2001","journal-title":"Am. J. Neuroradiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1161\/01.STR.31.8.1904","article-title":"Cerebral hemodynamics in CADASIL before and after acetazolamide challenge assessed with MRI bolus tracking","volume":"31","author":"Chabriat","year":"2000","journal-title":"Stroke"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1161\/01.STR.0000124124.69842.2d","article-title":"Cerebral blood flow and glucose metabolism studies on young CADASIL subjects","volume":"35","author":"Tuominen","year":"2004","journal-title":"Stroke"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1161\/01.STR.32.1.17","article-title":"Reduced cerebrovascular CO2 reactivity in CADASIL: A transcranial Doppler sonography study","volume":"32","author":"Pfefferkorn","year":"2001","journal-title":"Stroke"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1161\/hs0202.102949","article-title":"Prolonged cerebral transit time in CADASIL: A transcranial ultrasound study","volume":"33","author":"Liebetrau","year":"2002","journal-title":"Stroke"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1097\/01.WCB.0000062341.61367.D3","article-title":"Cerebral hemodynamics and white matter hyperintensities in CADASIL","volume":"23","author":"LesnikOberstein","year":"2003","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Ling, C., Fang, X., Kong, Q., Sun, Y., Wang, B., Zhuo, Y., An, J., Zhang, W., Wang, Z., and Zhang, Z. (2019). Lenticulostriate Arteries and Basal Ganglia Changes in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy, a High-Field MRI Study. Front. Neurol., 10.","DOI":"10.3389\/fneur.2019.00870"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2242","DOI":"10.1161\/01.STR.0000236838.84150.c2","article-title":"Arterioles of the lenticular nucleus in CADASIL","volume":"37","author":"Miao","year":"2006","journal-title":"Stroke"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1161\/STROKEAHA.108.528299","article-title":"Neuropathological correlates of temporal pole white matter hyperintensities in CADASIL","volume":"40","author":"Yamamoto","year":"2009","journal-title":"Stroke"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"108294","DOI":"10.1016\/j.jstrokecerebrovasdis.2025.108294","article-title":"Assessing changes on large cerebral arteries in CADASIL: Preliminary insights from a case-control analysis","volume":"34","author":"Mayer","year":"2025","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S0022-510X(03)00109-6","article-title":"Genetic, clinical and pathological studies of cadasil in Japan: A partial contribution of Notch3 mutations and implications of smooth muscle cell degeneration for the pathogenesis","volume":"212","author":"Santa","year":"2003","journal-title":"J. Neurol. Sci."},{"key":"ref_56","first-page":"910","article-title":"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy\u2014Report of an autopsied Japanese case","volume":"37","author":"Nishio","year":"1997","journal-title":"Clin. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1212\/01.wnl.0000180965.79209.50","article-title":"Large cerebral artery involvement in cadasil","volume":"65","author":"Choi","year":"2005","journal-title":"Neurology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1001\/archneur.59.9.1480","article-title":"CADASIL mimicking primary angiitis of the central nervous system","volume":"59","author":"Engelter","year":"2002","journal-title":"Arch. Neurol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/S0967-5868(02)00264-3","article-title":"Racial distribution of intracranial and extracranial atherosclerosis","volume":"10","author":"Li","year":"2003","journal-title":"J. Clin. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1212\/WNL.50.3.812","article-title":"Intracranial stenosis in Chinese patients with acute stroke","volume":"50","author":"Wong","year":"1998","journal-title":"Neurology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1159\/000106982","article-title":"Risk factors of intracranial cerebral atherosclerosis among asymptomatics","volume":"24","author":"Bae","year":"2007","journal-title":"Cerebrovasc. Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1097\/00004872-200109000-00002","article-title":"Prevalence, awareness, treatment, control and risk factors of hypertension in Korea: The ANASAN Study","volume":"19","author":"Jo","year":"2001","journal-title":"J. Hypertens."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1093\/brain\/awh223","article-title":"The influence of genetic and cardiovascular risk factors on the CADASIL phenotype","volume":"127","author":"Singhal","year":"2004","journal-title":"Brain"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"585","DOI":"10.3109\/00207454.2014.951929","article-title":"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: Phenotypic and mutational spectrum in patients from mainland China","volume":"125","author":"Yin","year":"2014","journal-title":"Int. J. Neurosci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s00415-009-0091-3","article-title":"Population-specific spectrum of NOTCH3 mutations, MRI features and founder effect of CADASIL in Chinese","volume":"256","author":"Lee","year":"2009","journal-title":"J. Neurol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Zhang, C., Li, W., Li, S., Niu, S., Wang, X., Yu, X., and Zhang, Z. (2020). Intracranial Large Artery Abnormalities and Association with Cerebral Small Vessel Disease in CADASIL. Front. Neurol., 11.","DOI":"10.3389\/fneur.2020.00726"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3313","DOI":"10.1161\/STROKEAHA.112.658500","article-title":"Risk factors and stroke mechanisms in atherosclerotic stroke: Intracranial compared with extracranial and anterior compared with posterior circulation disease","volume":"43","author":"Kim","year":"2012","journal-title":"Stroke"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1002\/ana.27004","article-title":"Medium and Large Artery Aneurysms in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy","volume":"96","author":"Tan","year":"2024","journal-title":"Ann. Neurol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"747","DOI":"10.4103\/aian.aian_903_21","article-title":"Fusiform Intracranial Aneurysms in a CADASIL Patient: A Possibly Missed Association","volume":"25","author":"Agarwal","year":"2022","journal-title":"Ann. Indian Acad. Neurol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"H2429","DOI":"10.1152\/ajpheart.00100.2007","article-title":"Involvement of MMPs in the outward remodeling of collateral mesenteric arteries","volume":"293","author":"Haas","year":"2007","journal-title":"Am. J. Physiol. Heart Circulat. Physiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1098\/rsif.2005.0073","article-title":"Hyperelastic modelling of arterial layers with distributed collagen fibre orientations","volume":"3","author":"Gasser","year":"2006","journal-title":"J. R. Soc. Interface"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1111\/j.1440-1789.2012.01358.x","article-title":"The contribution of HIV infection to intracranial arterial remodeling: A pilot study","volume":"33","author":"Gutierrez","year":"2013","journal-title":"Neuropathology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.jvs.2003.10.058","article-title":"Arterial enlargement, tortuosity, and intimal thickening in response to sequential exposure to high and low wall shear stress","volume":"39","author":"Sho","year":"2004","journal-title":"J. Vasc. Surg."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1093\/infdis\/jiw385","article-title":"Metalloproteinases and brain arterial remodeling among individuals with and those without HIV infection","volume":"214","author":"Gutierrez","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_75","first-page":"415","article-title":"Brain large artery inflammation associated with HIV and large artery remodeling","volume":"30","author":"Gutierrez","year":"2016","journal-title":"AIDS"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1016\/j.neuron.2014.07.034","article-title":"Sensory-related neural activity regulates the structure of vascular networks in the cerebral cortex","volume":"83","author":"Lacoste","year":"2014","journal-title":"Neuron"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1161\/STROKEAHA.116.015630","article-title":"Histopathological differences between the anterior and posterior brain arteries as a function of aging","volume":"48","author":"Roth","year":"2017","journal-title":"Stroke"},{"key":"ref_78","first-page":"1587","article-title":"Parallel and spiral flow patterns of vertebral artery contributions to the basilar artery","volume":"16","author":"Smith","year":"1995","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"ATP152","DOI":"10.1161\/str.45.suppl_1.tp152","article-title":"Correlates of dolichoectasia in an urban, stroke-free cohort: Results from the Northern Manhattan study","volume":"45","author":"Gutierrez","year":"2014","journal-title":"Stroke"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1177\/19714009231224429","article-title":"Association of brain arterial diameters with demographic and anatomical factors in a multi-national pooled analysis of cohort studies","volume":"37","author":"Khasiyev","year":"2024","journal-title":"Neuroradiol. J."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s12199-015-0498-7","article-title":"A new horizon of moyamoya disease and associated health risks explored through RNF213","volume":"21","author":"Koizumi","year":"2016","journal-title":"Environ. Health Prev. Med."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Liu, W., Morito, D., Takashima, S., Mineharu, Y., Kobayashi, H., Hitomi, T., Hashikata, H., Matsuura, N., Yamazaki, S., and Toyoda, A. (2011). Identification of RNF213 as a susceptibility gene for moyamoya disease and its possible role in vascular development. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0022542"},{"key":"ref_83","first-page":"245","article-title":"Research Committee on the Pathology and Treatment of Spontaneous Occlusion of the Circle of Willis; Health Labour Sciences Research Grant for Research on Measures for Infractable Diseases. Guidelines for diagnosis and treatment of moyamoya disease (spontaneous occlusion of the circle of Willis)","volume":"52","author":"Hashimoto","year":"2012","journal-title":"Neurol. Med. Chir."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/jhg.2010.132","article-title":"A genome-wide association study identifies RNF213 as the first Moyamoya disease gene","volume":"56","author":"Kamada","year":"2011","journal-title":"J. Hum. Genet."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Lin, J., and Sheng, W. (2018). RNF213 variant diversity predisposes distinct populations to dissimilar cerebrovascular diseases. BioMed Res. Int., 2018.","DOI":"10.1155\/2018\/6359174"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1007\/s00438-016-1172-5","article-title":"The association between the ring finger protein 213 (RNF213) polymorphisms and moyamoya disease susceptibility: A meta-analysis based on case-control studies","volume":"291","author":"Sun","year":"2016","journal-title":"Mol. Genet. Genom."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1038\/ejhg.2017.92","article-title":"Rare RNF213 variants in the C-terminal region encompassing the RING-finger domain are associated with moyamoya angiopathy in Caucasians","volume":"25","author":"Guey","year":"2017","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2894","DOI":"10.1161\/STROKEAHA.113.002477","article-title":"Genetic variant RNF213 c.14576G>A in various phenotypes of intracranial major artery stenosis\/occlusion","volume":"44","author":"Miyawaki","year":"2013","journal-title":"Stroke"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s12199-017-0680-1","article-title":"Rare variants of RNF213 and moyamoya\/non-moyamoya intracranial artery stenosis\/occlusion disease risk: A meta-analysis and systematic review. Environ","volume":"22","author":"Liao","year":"2017","journal-title":"Health Prev. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"E2","DOI":"10.3171\/2021.5.FOCUS21182","article-title":"Role of RNF213 polymorphism in defining quasi-moyamoya disease and definitive moyamoya disease","volume":"51","author":"Ishisaka","year":"2021","journal-title":"Neurosurg. Focus"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2453","DOI":"10.1002\/ajmg.a.37829","article-title":"Homozygosity for moyamoya disease risk allele leads to moyamoya disease with extracranial systemic and pulmonary vasculopathy","volume":"170","author":"Fukushima","year":"2016","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1007\/s12975-019-00743-6","article-title":"Moyamoya Disease and Spectrums of RNF213 Vasculopathy","volume":"11","author":"Bang","year":"2020","journal-title":"Transl. Stroke Res."},{"key":"ref_93","first-page":"e002317","article-title":"Genomic comparison with supercentenarians identifies RNF213 as a risk gene for pulmonary arterial hypertension. Circ. Genom","volume":"11","author":"Suzuki","year":"2018","journal-title":"Precis. Med."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Hiraide, T., Suzuki, H., Momoi, M., Shinya, Y., Fukuda, K., Kosaki, K., and Kataoka, M. (2022). RNF213-Associated Vascular Disease: A Concept Unifying Various Vasculopathies. Life, 12.","DOI":"10.3390\/life12040555"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.chest.2017.09.023","article-title":"Nonsyndromic peripheral pulmonary artery stenosis is associated with homozygosity of RNF213 p.Arg4810Lys regardless of cooccurrence of moyamoya disease","volume":"153","author":"Chang","year":"2018","journal-title":"Chest"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2638","DOI":"10.1016\/j.jstrokecerebrovasdis.2017.06.043","article-title":"Genetic Analysis of Ring Finger Protein 213 (RNF213) c.14576G>A in Intracranial Atherosclerosis of the Anterior and Posterior Circulations","volume":"26","author":"Shinya","year":"2017","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1161\/STROKEAHA.120.029527","article-title":"Association of Genetic Variants with Moyamoya Disease in 13,000 Individuals: A Meta-Analysis","volume":"51","author":"Wang","year":"2020","journal-title":"Stroke"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1016\/j.ajhg.2016.09.001","article-title":"RNF213 Is Associated with Intracranial Aneurysms in the French-Canadian Population","volume":"99","author":"Zhou","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3371","DOI":"10.1161\/STROKEAHA.112.663864","article-title":"Identification of a genetic variant common to moyamoya disease and intracranial major artery stenosis\/occlusion","volume":"43","author":"Miyawaki","year":"2012","journal-title":"Stroke"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"UCAS Japan Investigators (2012). The Natural Course of Unruptured Cerebral Aneurysms in a Japanese Cohort. N. Engl. J. Med., 366, 2474\u20132482.","DOI":"10.1056\/NEJMoa1113260"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.clineuro.2014.11.010","article-title":"Neoplastic cerebral aneurysm from metastatic tumor: A systematic review of clinical and treatment characteristics","volume":"128","author":"Zheng","year":"2015","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1159\/000015864","article-title":"Frequency and clinical correlates of occlusive lesions of cerebral arteries in Japanese patients without stroke","volume":"8","author":"Uehara","year":"1998","journal-title":"Cerebrovasc. Dis."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"e200176","DOI":"10.1212\/NXG.0000000000200176","article-title":"Blended Phenotype of NOTCH3 and RNF213 Variants With Accelerated Large and Small Artery Crosstalk: A Case Report and Literature Review","volume":"10","author":"Saito","year":"2024","journal-title":"Neurol. Genet."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/S1474-4422(22)00165-X","article-title":"Moyamoya disease: Diagnosis and interventions","volume":"21","author":"Ihara","year":"2022","journal-title":"Lancet Neurol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1161\/CIRCULATIONAHA.118.038439","article-title":"Moyamoya disease susceptibility variant RNF213 p.R4810K increases the risk of ischemic stroke attributable to large-artery atherosclerosis","volume":"139","author":"Okazaki","year":"2019","journal-title":"Circulation"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Zedde, M., and Pascarella, R. (2025). ABCC6 Involvement in Cerebral Small Vessel Disease: Potential Mechanisms and Associations. Genes, 16.","DOI":"10.3390\/genes16070728"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1177\/23969873221144089","article-title":"European Stroke Organisation (ESO) Guidelines on Moyamoya angiopathy Endorsed by Vascular European Reference Network (VASCERN)","volume":"8","author":"Bersano","year":"2023","journal-title":"Eur. Stroke J."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/8\/882\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:16:41Z","timestamp":1760033801000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/8\/882"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,26]]},"references-count":107,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["genes16080882"],"URL":"https:\/\/doi.org\/10.3390\/genes16080882","relation":{},"ISSN":["2073-4425"],"issn-type":[{"type":"electronic","value":"2073-4425"}],"subject":[],"published":{"date-parts":[[2025,7,26]]}}}