{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T18:24:39Z","timestamp":1772648679663,"version":"3.50.1"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21KK0201"],"award-info":[{"award-number":["21KK0201"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K07887"],"award-info":[{"award-number":["22K07887"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Clin Immunol"],"DOI":"10.1007\/s10875-026-01988-1","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T16:01:23Z","timestamp":1772640083000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Two Cases of CLIPPERS-like Syndrome Sharing a Hypomorphic UNC13D Variant"],"prefix":"10.1007","volume":"46","author":[{"given":"Hirotaka","family":"Sagawa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kosei","family":"Hirata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saori","family":"Katayama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirofumi","family":"Shibata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Etsushi","family":"Toyofuku","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuya","family":"Kaneko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Katata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusuke","family":"Takezawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsugu","family":"Uematsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iichiroh","family":"Onishi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuto","family":"Yamazaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takaaki","family":"Hattori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahide","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaki","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kohsuke","family":"Imai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Yasumi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohiro","family":"Morio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takanori","family":"Yokota","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoji","family":"Sasahara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirokazu","family":"Kanegane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"1988_CR1","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.blre.2014.03.002","volume":"28","author":"GE Janka","year":"2014","unstructured":"Janka GE, Lehmberg K. Hemophagocytic syndromes\u2013an update. Blood Rev. 2014;28:135\u201342. https:\/\/doi.org\/10.1016\/j.blre.2014.03.002.","journal-title":"Blood Rev"},{"key":"1988_CR2","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1007\/s11926-014-0439-2","volume":"16","author":"M Zhang","year":"2014","unstructured":"Zhang M, Behrens EM, Atkinson TP, et al. Genetic defects in cytolysis in macrophage activation syndrome. Curr Rheumatol Rep. 2014;16:439. https:\/\/doi.org\/10.1007\/s11926-014-0439-2.","journal-title":"Curr Rheumatol Rep"},{"key":"1988_CR3","doi-asserted-by":"publisher","first-page":"2626","DOI":"10.1093\/brain\/awq164","volume":"133","author":"SJ Pittock","year":"2010","unstructured":"Pittock SJ, Debruyne J, Krecke KN, et al. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Brain. 2010;133:2626\u201334. https:\/\/doi.org\/10.1093\/brain\/awq164.","journal-title":"Brain"},{"key":"1988_CR4","doi-asserted-by":"publisher","first-page":"e560","DOI":"10.1212\/NXI.0000000000000560","volume":"6","author":"LA Benson","year":"2019","unstructured":"Benson LA, Li H, Henderson LA, et al. Pediatric CNS-isolated hemophagocytic lymphohistiocytosis. Neurol Neuroimmunol Neuroinflamm. 2019;6:e560. https:\/\/doi.org\/10.1212\/NXI.0000000000000560.","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"1988_CR5","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1177\/13524585211053565","volume":"28","author":"A Parida","year":"2022","unstructured":"Parida A, Abdel-Mannan O, Mankad K, et al. Isolated central nervous system familial hemophagocytic lymphohistiocytosis (fHLH) presenting as a mimic of demyelination in children. Mult Scler. 2022;28:669\u201375. https:\/\/doi.org\/10.1177\/13524585211053565.","journal-title":"Mult Scler"},{"issue":"9","key":"1988_CR6","doi-asserted-by":"publisher","first-page":"e30482","DOI":"10.1002\/pbc.30482","volume":"70","author":"M Henry","year":"2023","unstructured":"Henry M, Altinok D, Williams MT, et al. Isolated central nervous system hemophagocytic lymphohistiocytosis caused by novel UNC13D mutation. Pediatr Blood Cancer. 2023;e30482. https:\/\/doi.org\/10.1002\/pbc.30482.","journal-title":"Pediatr Blood Cancer"},{"key":"1988_CR7","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000970","author":"G Taieb","year":"2021","unstructured":"Taieb G, Kaphan E, Duflos C, et al. Hemophagocytic lymphohistiocytosis gene mutations in adult patients presenting with CLIPPERS-like syndrome. Neurol Neuroimmunol Neuroinflamm. 2021. https:\/\/doi.org\/10.1212\/NXI.0000000000000970.","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"1988_CR8","doi-asserted-by":"publisher","first-page":"2893","DOI":"10.1007\/s00415-024-12241-3","volume":"271","author":"B Lemarchant","year":"2024","unstructured":"Lemarchant B, de Saint Basile G, Zephir H, et al. Familial hemophagocytic lymphohistiocytosis: from macrophage activation syndrome to CLIPPERS. J Neurol. 2024;271:2893\u20137. https:\/\/doi.org\/10.1007\/s00415-024-12241-3.","journal-title":"J Neurol"},{"key":"1988_CR9","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1111\/j.1365-2141.2007.06922.x","volume":"140","author":"A Horne","year":"2008","unstructured":"Horne A, Trottestam H, Arico M, et al. Frequency and spectrum of central nervous system involvement in 193 children with haemophagocytic lymphohistiocytosis. Br J Haematol. 2008;140:327\u201335. https:\/\/doi.org\/10.1111\/j.1365-2141.2007.06922.x.","journal-title":"Br J Haematol"},{"key":"1988_CR10","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1007\/s10875-016-0357-3","volume":"37","author":"M Hori","year":"2017","unstructured":"Hori M, Yasumi T, Shimodera S, et al. A CD57(+) CTL degranulation assay effectively identifies familial hemophagocytic lymphohistiocytosis type 3 patients. J Clin Immunol. 2017;37:92\u20139. https:\/\/doi.org\/10.1007\/s10875-016-0357-3.","journal-title":"J Clin Immunol"},{"key":"1988_CR11","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.1182\/blood-2011-01-329540","volume":"118","author":"Y Murata","year":"2011","unstructured":"Murata Y, Yasumi T, Shirakawa R, et al. Rapid diagnosis of FHL3 by flow cytometric detection of intraplatelet Munc13-4 protein. Blood. 2011;118:1225\u201330. https:\/\/doi.org\/10.1182\/blood-2011-01-329540.","journal-title":"Blood"},{"key":"1988_CR12","doi-asserted-by":"publisher","first-page":"2016","DOI":"10.1182\/blood-2017-10-812503","volume":"131","author":"H Shibata","year":"2018","unstructured":"Shibata H, Yasumi T, Shimodera S, et al. Human CTL-based functional analysis shows the reliability of a munc13-4 protein expression assay for FHL3 diagnosis. Blood. 2018;131:2016\u201325. https:\/\/doi.org\/10.1182\/blood-2017-10-812503.","journal-title":"Blood"},{"key":"1988_CR13","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1001\/archneurol.2012.122","volume":"69","author":"G Taieb","year":"2012","unstructured":"Taieb G, Duflos C, Renard D, et al. Long-term outcomes of CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) in a consecutive series of 12 patients. Arch Neurol. 2012;69:847\u201355. https:\/\/doi.org\/10.1001\/archneurol.2012.122.","journal-title":"Arch Neurol"},{"key":"1988_CR14","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1136\/jnnp-2011-301054","volume":"83","author":"NG Simon","year":"2012","unstructured":"Simon NG, Parratt JD, Barnett MH, et al. Expanding the clinical, radiological and neuropathological phenotype of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). J Neurol Neurosurg Psychiatry. 2012;83:15\u201322. https:\/\/doi.org\/10.1136\/jnnp-2011-301054.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"1988_CR15","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1002\/eji.201646686","volume":"47","author":"S Ammann","year":"2017","unstructured":"Ammann S, Lehmberg K, Zur Stadt U, et al. Primary and secondary hemophagocytic lymphohistiocytosis have different patterns of T-cell activation, differentiation and repertoire. Eur J Immunol. 2017;47:364\u201373. https:\/\/doi.org\/10.1002\/eji.201646686.","journal-title":"Eur J Immunol"},{"key":"1988_CR16","doi-asserted-by":"publisher","first-page":"2415","DOI":"10.1093\/brain\/awx200","volume":"140","author":"WO Tobin","year":"2017","unstructured":"Tobin WO, Guo Y, Krecke KN, et al. Diagnostic criteria for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Brain. 2017;140:2415\u201325. https:\/\/doi.org\/10.1093\/brain\/awx200.","journal-title":"Brain"},{"key":"1988_CR17","doi-asserted-by":"publisher","first-page":"4577","DOI":"10.1182\/blood-2011-06-356261","volume":"118","author":"H Trottestam","year":"2011","unstructured":"Trottestam H, Horne A, Arico M, et al. Chemoimmunotherapy for hemophagocytic lymphohistiocytosis: long-term results of the HLH-94 treatment protocol. Blood. 2011;118:4577\u201384. https:\/\/doi.org\/10.1182\/blood-2011-06-356261.","journal-title":"Blood"},{"key":"1988_CR18","doi-asserted-by":"publisher","first-page":"2728","DOI":"10.1182\/blood-2017-06-788349","volume":"130","author":"E Bergsten","year":"2017","unstructured":"Bergsten E, Horne A, Arico M, et al. Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study. Blood. 2017;130:2728\u201338. https:\/\/doi.org\/10.1182\/blood-2017-06-788349.","journal-title":"Blood"},{"key":"1988_CR19","doi-asserted-by":"publisher","first-page":"e8377","DOI":"10.1002\/ccr3.8377","volume":"12","author":"AK Shervedani","year":"2024","unstructured":"Shervedani AK, Tabibian F, Khotbesara MG, et al. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids triggered by Hodgkin\u2019s lymphoma: a case report and brief literature review. Clin Case Rep. 2024;12:e8377. https:\/\/doi.org\/10.1002\/ccr3.8377.","journal-title":"Clin Case Rep"},{"key":"1988_CR20","doi-asserted-by":"publisher","first-page":"9809","DOI":"10.1073\/pnas.0903815106","volume":"106","author":"JYK Chia","year":"2009","unstructured":"Chia JYK, Whisstock JC, Dunstone MA, Trapani JA, Voskoboinik I. Temperature sensitivity of human perforin mutants unmasks subtotal loss of cytotoxicity, delayed FHL, and a predisposition to cancer. Proc Natl Acad Sci U S A. 2009;106:9809\u201314. https:\/\/doi.org\/10.1073\/pnas.0903815106.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1988_CR21","doi-asserted-by":"publisher","first-page":"1365975","DOI":"10.3389\/fimmu.2024.1365975","volume":"15","author":"C Wei","year":"2024","unstructured":"Wei C, Zhao D, Xue S, et al. Germline defects of familial hemophagocytic lymphohistiocytosis-related genes presenting as adult-onset peripheral T-cell lymphoma. Front Immunol. 2024;15:1365975. https:\/\/doi.org\/10.3389\/fimmu.2024.1365975.","journal-title":"Front Immunol"},{"key":"1988_CR22","doi-asserted-by":"publisher","first-page":"2578","DOI":"10.1182\/bloodadvances.2020001605","volume":"4","author":"V Gadoury-Levesque","year":"2020","unstructured":"Gadoury-Levesque V, Dong L, Su R, et al. Frequency and spectrum of disease-causing variants in 1892 patients with suspected genetic HLH disorders. Blood Adv. 2020;4:2578\u201394. https:\/\/doi.org\/10.1182\/bloodadvances.2020001605.","journal-title":"Blood Adv"},{"key":"1988_CR23","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1136\/jmg.2010.085456","volume":"48","author":"E Sieni","year":"2011","unstructured":"Sieni E, Cetica V, Santoro A, et al. Genotype-phenotype study of familial haemophagocytic lymphohistiocytosis type 3. J Med Genet. 2011;48:343\u201352. https:\/\/doi.org\/10.1136\/jmg.2010.085456.","journal-title":"J Med Genet"},{"key":"1988_CR24","doi-asserted-by":"publisher","first-page":"5794","DOI":"10.1182\/blood-2011-07-370148","volume":"118","author":"K Zhang","year":"2011","unstructured":"Zhang K, Jordan MB, Marsh RA, et al. Hypomorphic mutations in PRF1, MUNC13-4, and STXBP2 are associated with adult-onset familial HLH. Blood. 2011;118:5794\u20138. https:\/\/doi.org\/10.1182\/blood-2011-07-370148.","journal-title":"Blood"},{"key":"1988_CR25","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1136\/jmg.2006.041863","volume":"43","author":"A Santoro","year":"2006","unstructured":"Santoro A, Cannella S, Bossi G, et al. Novel Munc13-4 mutations in children and young adult patients with haemophagocytic lymphohistiocytosis. J Med Genet. 2006;43:953\u201360. https:\/\/doi.org\/10.1136\/jmg.2006.041863.","journal-title":"J Med Genet"},{"key":"1988_CR26","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1136\/jmg.2007.054288","volume":"45","author":"E Rudd","year":"2008","unstructured":"Rudd E, Bryceson YT, Zheng C, et al. Spectrum, and clinical and functional implications of UNC13D mutations in familial haemophagocytic lymphohistiocytosis. J Med Genet. 2008;45:134\u201341. https:\/\/doi.org\/10.1136\/jmg.2007.054288.","journal-title":"J Med Genet"},{"key":"1988_CR27","doi-asserted-by":"publisher","first-page":"e14136","DOI":"10.1111\/pai.14136","volume":"35","author":"Q Zhao","year":"2024","unstructured":"Zhao Q, Zhao Q, Tang X, et al. Atypical familial hemophagocytic lymphohistiocytosis type 3 in children: a report of cases and literature review. Pediatr Allergy Immunol. 2024;35:e14136. https:\/\/doi.org\/10.1111\/pai.14136.","journal-title":"Pediatr Allergy Immunol"},{"key":"1988_CR28","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1016\/j.transproceed.2024.05.011","volume":"56","author":"D Akiyama","year":"2024","unstructured":"Akiyama D, Kanda J, Hanyu Y, et al. Successful second CBT for graft failure after first CBT for adult-onset familial hemophagocytic lymphohistiocytosis type 3: a case report. Transplant Proc. 2024;56:1205\u20139. https:\/\/doi.org\/10.1016\/j.transproceed.2024.05.011.","journal-title":"Transplant Proc"},{"key":"1988_CR29","doi-asserted-by":"publisher","first-page":"2080","DOI":"10.3324\/haematol.2010.029389","volume":"95","author":"J Rohr","year":"2010","unstructured":"Rohr J, Beutel K, Maul-Pavicic A, et al. Atypical familial hemophagocytic lymphohistiocytosis due to mutations in UNC13D and STXBP2 overlaps with primary immunodeficiency diseases. Haematologica. 2010;95:2080\u20137. https:\/\/doi.org\/10.3324\/haematol.2010.029389.","journal-title":"Haematologica"},{"key":"1988_CR30","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1001\/jamaneurol.2022.2141","volume":"79","author":"X Ayrignac","year":"2022","unstructured":"Ayrignac X, Carra-Dalliere C, Marelli C, et al. Adult-onset genetic central nervous system disorders masquerading as acquired neuroinflammatory disorders: a review. JAMA Neurol. 2022;79:1069\u201378. https:\/\/doi.org\/10.1001\/jamaneurol.2022.2141.","journal-title":"JAMA Neurol"},{"key":"1988_CR31","doi-asserted-by":"publisher","first-page":"1604","DOI":"10.3174\/ajnr.A7194","volume":"42","author":"ES Hoogeveen","year":"2021","unstructured":"Hoogeveen ES, Pelzer N, de Boer I, et al. Neuroimaging findings in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations. AJNR Am J Neuroradiol. 2021;42:1604\u20139. https:\/\/doi.org\/10.3174\/ajnr.A7194.","journal-title":"AJNR Am J Neuroradiol"},{"key":"1988_CR32","doi-asserted-by":"publisher","first-page":"5551","DOI":"10.1172\/JCI135947","volume":"130","author":"MK Schindler","year":"2020","unstructured":"Schindler MK, Pittaluga S, Enose-Akahata Y, et al. Haploinsufficiency of immune checkpoint receptor CTLA4 induces a distinct neuroinflammatory disorder. J Clin Invest. 2020;130:5551\u201361. https:\/\/doi.org\/10.1172\/JCI135947.","journal-title":"J Clin Invest"},{"key":"1988_CR33","doi-asserted-by":"publisher","first-page":"2321","DOI":"10.1093\/brain\/awn178","volume":"131","author":"D Pareyson","year":"2008","unstructured":"Pareyson D, Fancellu R, Mariotti C, et al. Adult-onset Alexander disease: a series of eleven unrelated cases with review of the literature. Brain. 2008;131:2321\u201331. https:\/\/doi.org\/10.1093\/brain\/awn178.","journal-title":"Brain"},{"key":"1988_CR34","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1002\/jdn.10003","volume":"80","author":"BR Turk","year":"2020","unstructured":"Turk BR, Theda C, Fatemi A, et al. X-linked adrenoleukodystrophy: pathology, pathophysiology, diagnostic testing, newborn screening and therapies. Int J Dev Neurosci. 2020;80:52\u201372. https:\/\/doi.org\/10.1002\/jdn.10003.","journal-title":"Int J Dev Neurosci"}],"container-title":["Journal of Clinical Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10875-026-01988-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10875-026-01988-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10875-026-01988-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T16:01:23Z","timestamp":1772640083000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10875-026-01988-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,4]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1988"],"URL":"https:\/\/doi.org\/10.1007\/s10875-026-01988-1","relation":{},"ISSN":["1573-2592"],"issn-type":[{"value":"1573-2592","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,4]]},"assertion":[{"value":"16 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Genetic analysis was performed after obtaining written informed consent from all patients. This study was performed in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of Institute of Science Tokyo and Tohoku University.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Informed consent was obtained from all patients and their parents included in this study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent To Participate"}},{"value":"Informed consent was obtained from all participants included in this study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent To Publish"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"23"}}