{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:02:15Z","timestamp":1791302535598,"version":"4.1.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      A founder variant of\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">RNF<\/jats:styled-content>\n                        213\n                      <\/jats:italic>\n                      , p.R4810K (c.14429G&gt;A, rs112735431), was recently identified as a major genetic risk factor for moyamoya disease (\n                      <jats:styled-content style=\"fixed-case\">MMD<\/jats:styled-content>\n                      ) in Japan. Although the association of p.R4810K was reported to be highly significant and reproducible, the disease susceptibility of other\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">RNF<\/jats:styled-content>\n                        213\n                      <\/jats:italic>\n                      variants remains largely unknown. In the present study, we systematically evaluated the coding variants detected in Japanese patients and controls for associations with\n                      <jats:styled-content style=\"fixed-case\">MMD<\/jats:styled-content>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      To detect variants of\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">RNF<\/jats:styled-content>\n                        213\n                      <\/jats:italic>\n                      , all coding exons were sequenced in 27 Japanese\n                      <jats:styled-content style=\"fixed-case\">MMD<\/jats:styled-content>\n                      patients without p.R4810K. We also validated all previously reported variants in our case\u2013control samples and tested for associations in combination with previous Japanese study cohorts, including the 1000 Genomes Project data set, as population\u2010based controls. Forty\u2010six missense variants other than p.R4810K were identified among 370 combined patients and 279 combined controls in Japan. Sixteen of 46 variants were polymorphisms with minor allele frequency &gt;1%, and, after conditioning on the p.R4810K genotype, were not associated with\n                      <jats:styled-content style=\"fixed-case\">MMD<\/jats:styled-content>\n                      . We conducted a variable threshold test using Combined Annotation\u2010Dependent Depletion on the remaining 30 rare variants (minor allele frequency &lt;1%), and the results showed that the frequency of potentially functional variants was significantly higher in patients than in controls (permutation, minimum\n                      <jats:italic>P<\/jats:italic>\n                      =0.045).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Not only p.4810K but also other functional missense variants of\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">RNF<\/jats:styled-content>\n                        213\n                      <\/jats:italic>\n                      conferred susceptibility to\n                      <jats:styled-content style=\"fixed-case\">MMD<\/jats:styled-content>\n                      . Our analysis also revealed that \u224820% of Japanese\n                      <jats:styled-content style=\"fixed-case\">MMD<\/jats:styled-content>\n                      patients did not harbor susceptibility variants of\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">RNF<\/jats:styled-content>\n                        213\n                      <\/jats:italic>\n                      , indicating the presence of other susceptibility genes for\n                      <jats:styled-content style=\"fixed-case\">MMD<\/jats:styled-content>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.115.001862","type":"journal-article","created":{"date-parts":[[2015,5,11]],"date-time":"2015-05-11T22:31:57Z","timestamp":1431383517000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":67,"title":["Systematic Validation of\n                    <i>RNF213<\/i>\n                    Coding Variants in Japanese Patients With Moyamoya Disease"],"prefix":"10.1161","volume":"4","author":[{"given":"Yosuke","family":"Moteki","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Neurological Institute Tokyo Women's Medical University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Onda","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Neurological Institute Tokyo Women's Medical University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetoshi","family":"Kasuya","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Medical Center East Tokyo Women's Medical University Tokyo Japan"},{"name":"Tokyo Women's Medical University Institute for Integrated Medical Sciences (TIIMS) Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taku","family":"Yoneyama","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Neurological Institute Tokyo Women's Medical University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshikazu","family":"Okada","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Neurological Institute Tokyo Women's Medical University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kengo","family":"Hirota","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Medical Center East Tokyo Women's Medical University Tokyo Japan"},{"name":"Tokyo Women's Medical University Institute for Integrated Medical Sciences (TIIMS) Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maki","family":"Mukawa","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Tokyo Medical and Dental University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Nariai","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Tokyo Medical and Dental University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shohei","family":"Mitani","sequence":"additional","affiliation":[{"name":"Department of Physiology Tokyo Women's Medical University Tokyo Japan"},{"name":"Tokyo Women's Medical University Institute for Integrated Medical Sciences (TIIMS) Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Akagawa","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Medical Center East Tokyo Women's Medical University Tokyo Japan"},{"name":"Tokyo Women's Medical University Institute for Integrated Medical Sciences (TIIMS) Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1969.00480090076012"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1042-3680(18)30044-5"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.113.004386"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.107.490714"},{"key":"e_1_3_1_6_2","first-page":"141","volume-title":"The Research Committee on Spontaneous Occlusion of the Circle of Willis (Moyamoya Disease) of the Ministry of Health and Welfare Japan: Annual Report 1992","author":"Fukuyama Y","year":"1992","unstructured":"Fukuyama Y, Kanai N, Osawa M. Clinical genetic analysis on the moyamoya disease. In: Yonekawa Y, ed. The Research Committee on Spontaneous Occlusion of the Circle of Willis (Moyamoya Disease) of the Ministry of Health and Welfare Japan: Annual Report 1992. Tokyo, Japan: Ministry of Health and Welfare Japan; 1992:141\u2013146."},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-8467(97)00042-5"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2010.132"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022542"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318249f71f"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13127"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22225"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2892"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.04.005"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.04.004"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-8467(97)00082-6"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000291012.49986.f9"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11632"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1086\/429864"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01245622"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/16.2.182"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1086\/521987"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21517"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22376"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1229"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.114.006244"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1159\/000352065"},{"key":"e_1_3_1_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.02.015"},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2014.01.011"},{"key":"e_1_3_1_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.07.004"},{"key":"e_1_3_1_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.08.067"},{"key":"e_1_3_1_33_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.112.663864"},{"key":"e_1_3_1_34_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.113.002477"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.115.001862","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T06:35:43Z","timestamp":1715582143000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.115.001862"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,5]]},"references-count":33,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2015,5]]}},"alternative-id":["10.1161\/JAHA.115.001862"],"URL":"https:\/\/doi.org\/10.1161\/jaha.115.001862","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,5]]},"assertion":[{"value":"2015-03-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-04-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-05-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e001862"}}