{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T17:21:03Z","timestamp":1791652863416,"version":"4.3.4"},"reference-count":44,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,22]],"date-time":"2023-03-22T00:00:00Z","timestamp":1679443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Health Ministry","award":["RF-2019-12369247"],"award-info":[{"award-number":["RF-2019-12369247"]}]},{"name":"Italian Health Ministry","award":["Ricerca Corrente 2022"],"award-info":[{"award-number":["Ricerca Corrente 2022"]}]},{"name":"Italian Health Ministry","award":["5x1000-2017(5xMILR17)"],"award-info":[{"award-number":["5x1000-2017(5xMILR17)"]}]},{"name":"Finanziamento","award":["RF-2019-12369247"],"award-info":[{"award-number":["RF-2019-12369247"]}]},{"name":"Finanziamento","award":["Ricerca Corrente 2022"],"award-info":[{"award-number":["Ricerca Corrente 2022"]}]},{"name":"Finanziamento","award":["5x1000-2017(5xMILR17)"],"award-info":[{"award-number":["5x1000-2017(5xMILR17)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder caused by mutations in NF1 gene, coding for neurofibromin 1. NF1 can be associated with Moyamoya disease (MMD), and this association, typical of paediatric patients, is referred to as Moyamoya syndrome (MMS). MMD is a cerebral arteriopathy characterized by the occlusion of intracranial arteries and collateral vessel formation, which increase the risk of ischemic and hemorrhagic events. RNF213 gene mutations have been associated with MMD, so we investigated whether rare variants of RNF213 could act as genetic modifiers of MMS phenotype in a pediatric cohort of 20 MMS children, 25 children affected by isolated MMD and 47 affected only by isolated NF1. By next-generation re-sequencing (NGS) of patients\u2019 DNA and gene burden tests, we found that RNF213 seems to play a role only for MMD occurrence, while it does not appear to be involved in the increased risk of Moyamoya for MMS patients. We postulated that the loss of neurofibromin 1 can be enough for the excessive proliferation of vascular smooth muscle cells, causing Moyamoya arteriopathy associated with NF1. Further studies will be crucial to support these findings and to elucidate the possible role of other genes, enhancing our knowledge about pathogenesis and treatment of MMS.<\/jats:p>","DOI":"10.3390\/cancers15061916","type":"journal-article","created":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T02:35:26Z","timestamp":1679538926000},"page":"1916","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Moyamoya Vasculopathy in Neurofibromatosis Type 1 Pediatric Patients: The Role of Rare Variants of RNF213"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3698-9319","authenticated-orcid":false,"given":"Marzia","family":"Ognibene","sequence":"first","affiliation":[{"name":"U.O.C. Genetica Medica, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2194-7239","authenticated-orcid":false,"given":"Marcello","family":"Scala","sequence":"additional","affiliation":[{"name":"U.O.C. Genetica Medica, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"},{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Universit\u00e0 Degli Studi di Genova, 16145 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Iacomino","sequence":"additional","affiliation":[{"name":"U.O.C. Genetica Medica, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5460-2977","authenticated-orcid":false,"given":"Irene","family":"Schiavetti","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze della Salute, Universit\u00e0 di Genova, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7807-1322","authenticated-orcid":false,"given":"Francesca","family":"Madia","sequence":"additional","affiliation":[{"name":"U.O.C. Genetica Medica, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Traverso","sequence":"additional","affiliation":[{"name":"U.O.C. Neurologia Pediatrica e Malattie Muscolari, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Guerrisi","sequence":"additional","affiliation":[{"name":"U.O.C. Genetica Medica, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Di Duca","sequence":"additional","affiliation":[{"name":"U.O.C. Genetica Medica, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1828-6900","authenticated-orcid":false,"given":"Francesco","family":"Caroli","sequence":"additional","affiliation":[{"name":"U.O.C. Genetica Medica, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5304-3608","authenticated-orcid":false,"given":"Simona","family":"Baldassari","sequence":"additional","affiliation":[{"name":"U.O.C. Genetica Medica, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5971-0926","authenticated-orcid":false,"given":"Barbara","family":"Tappino","sequence":"additional","affiliation":[{"name":"LABSIEM (Laboratory for the Study of Inborn Errors of Metabolism), IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferruccio","family":"Romano","sequence":"additional","affiliation":[{"name":"U.O.C. Genomica e Genetica Clinica, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9524-8492","authenticated-orcid":false,"given":"Paolo","family":"Uva","sequence":"additional","affiliation":[{"name":"Unit\u00e0 di Bioinformatica Clinica, Direzione Scientifica, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Vozzi","sequence":"additional","affiliation":[{"name":"Genomic Facility, Istituto Italiano di Tecnologia, 16163 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2473-5282","authenticated-orcid":false,"given":"Cristina","family":"Chelleri","sequence":"additional","affiliation":[{"name":"U.O.C. 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