{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:01:35Z","timestamp":1791295295849,"version":"4.1.0"},"reference-count":10,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2016,7,4]],"date-time":"2016-07-04T00:00:00Z","timestamp":1467590400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16K09974"],"award-info":[{"award-number":["16K09974"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:sec><jats:label\/><jats:p>Moyamoya disease is characterized by diffuse distal intracranial stenosis. Recently, <jats:italic>RNF213<\/jats:italic> has been identified as a susceptibility gene in the development of this condition. Pulmonary hypertension is a rare progressive vasculopathy with an unknown etiology. The co\u2010occurrence of pulmonary hypertension and Moyamoya disease has been described in four patients; however, whether this co\u2010occurrence represents a chance association or a common vascular pathology has remained unknown. Here, we report two unrelated male patients who presented during their childhood with dyspnea on exertion. Systemic vascular imaging studies revealed the presence of pulmonary hypertension and Moyamoya disease in both patients. Medical exome sequencing revealed that both patients had a homozygous mutation for p.Arg4810Lys in <jats:italic>RNF213<\/jats:italic>. We suggest that homozygosity in <jats:italic>RNF213<\/jats:italic> may lead to a novel entity involving the brain and lung. Interestingly, when present in a heterozygous state, this mutation causes a classic cerebral vascular disease, Moyamoya disease. In the homozygous state, the exact same mutation led to Moyamoya disease with extracranial systemic vasculopathy in at least two patients. From a clinical standpoint, cerebrovascular or pulmonary vascular investigations may be warranted in patients with pulmonary hypertension or Moyamoya disease, respectively. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37829","type":"journal-article","created":{"date-parts":[[2016,7,4]],"date-time":"2016-07-04T05:43:19Z","timestamp":1467610999000},"page":"2453-2456","source":"Crossref","is-referenced-by-count":73,"title":["Homozygosity for moyamoya disease risk allele leads to moyamoya disease with extracranial systemic and pulmonary vasculopathy"],"prefix":"10.1002","volume":"170","author":[{"given":"Hiroyuki","family":"Fukushima","sequence":"first","affiliation":[{"name":"Department of Pediatrics Keio University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiki","family":"Takenouchi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Keio University School of Medicine Tokyo Japan"},{"name":"Center for Medical Genetics Keio University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenjiro","family":"Kosaki","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Keio University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,7,4]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa033277"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2010.132"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2008-1071486"},{"key":"e_1_2_6_5_1","first-page":"1","volume-title":"Vascular and interventional radiology: The requisites","author":"Kaufman JA","year":"2014"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.115.002146"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022542"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep04442"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1017\/S104795110600045X"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.10.035"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2012.05.002"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.37829","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.37829","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.37829","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T23:39:42Z","timestamp":1696635582000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.37829"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,7,4]]},"references-count":10,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2016,9]]}},"alternative-id":["10.1002\/ajmg.a.37829"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.37829","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7,4]]}}}