{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T22:16:18Z","timestamp":1780438578839,"version":"3.54.1"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,1,20]],"date-time":"2024-01-20T00:00:00Z","timestamp":1705708800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,1,20]],"date-time":"2024-01-20T00:00:00Z","timestamp":1705708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Application Foundation Program of Science and Technology Department of Sichuan Province","award":["2020YFS0253"],"award-info":[{"award-number":["2020YFS0253"]}]},{"name":"Application Foundation Program of Science and Technology Department of Sichuan Province","award":["2020YFS0253"],"award-info":[{"award-number":["2020YFS0253"]}]},{"name":"Application Foundation Program of Science and Technology Department of Sichuan Province","award":["2020YFS0253"],"award-info":[{"award-number":["2020YFS0253"]}]},{"name":"Application Foundation Program of Science and Technology Department of Sichuan Province","award":["2020YFS0253"],"award-info":[{"award-number":["2020YFS0253"]}]},{"name":"Application Foundation Program of Science and Technology Department of Sichuan Province","award":["2020YFS0253"],"award-info":[{"award-number":["2020YFS0253"]}]},{"name":"Application Foundation Program of Science and Technology Department of Sichuan Province","award":["2020YFS0253"],"award-info":[{"award-number":["2020YFS0253"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Pediatr"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Radioulnar synostosis with amegakaryocytic thrombocytopenia (RUSAT) type 2, caused by <jats:italic>MDS1 and EVI1 complex locus<\/jats:italic> (<jats:italic>MECOM<\/jats:italic>) gene mutations, is a rare inherited bone marrow failure syndrome (IBMFS) with skeletal anomalies, characterized by varying presentation of congenital thrombocytopenia (progressing to pancytopenia), bilateral proximal radioulnar synostosis, and other skeletal abnormalities. Due to limited knowledge and heterogenous manifestations, clinical diagnosis of the disease is challenging. Here we reported a novel <jats:italic>MECOM<\/jats:italic> mutation in a Chinese boy with typical clinical features for RUSAT-2. Trio-based whole exome sequencing of buccal swab revealed a novel heterozygous missense mutation in exon 11 of the <jats:italic>MECOM<\/jats:italic> gene (chr3:168818673; NM_001105078.3:c.2285G\u2009&gt;\u2009A). The results strongly suggest that the variant was a germline mutation and disease-causing mutation. The patient received matched unrelated donor hematopoetic stem cell transplantation (HSCT). This finding was not only expanded the pathogenic mutation spectrum of <jats:italic>MECOM<\/jats:italic> gene, but also provided key information for clinical diagnosis and treatment of RUSAT-2.<\/jats:p>","DOI":"10.1186\/s12887-024-04552-1","type":"journal-article","created":{"date-parts":[[2024,1,20]],"date-time":"2024-01-20T05:02:17Z","timestamp":1705726937000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A novel missense mutation in the MECOM gene in a Chinese boy with radioulnar synostosis with amegakaryocytic thrombocytopenia"],"prefix":"10.1186","volume":"24","author":[{"given":"Duowen","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiping","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongjun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxi","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,20]]},"reference":[{"issue":"9","key":"4552_CR1","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1136\/jmedgenet-2012-100990","volume":"49","author":"M Nielsen","year":"2012","unstructured":"Nielsen M, Vermont C, Aten E, et al. Deletion of the 3q26 region including the EVI1 and MDS1 genes in a neonate with congenital thrombocytopenia and subsequent aplastic anaemia. J Med Genet. 2012;49(9):598\u2013600.","journal-title":"J Med Genet"},{"key":"4552_CR2","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1182\/bloodadvances.2018016501","volume":"2","author":"M Germeshausen","year":"2018","unstructured":"Germeshausen M, Ancliff P, Estrada J, et al. MECOM-associated syndrome: a heterogeneous inherited bone marrow failure syn- drome with amegakaryocytic thrombocytopenia. Blood Adv. 2018;2:586\u201396.","journal-title":"Blood Adv"},{"key":"4552_CR3","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1016\/j.ajhg.2015.10.010","volume":"97","author":"T Niihori","year":"2015","unstructured":"Niihori T, Ouchi-Uchiyama M, Sasahara Y, et al. Mutations in MECOM, encodingoncoprotein EVI1, cause radioulnar synostosis with amegakaryocytic thrombocytopenia. Am J Hum Genet. 2015;97:848\u201354.","journal-title":"Am J Hum Genet"},{"key":"4552_CR4","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1182\/blood-2017-09-806489","volume":"131","author":"O Bluteau","year":"2018","unstructured":"Bluteau O, Sebert M, Leblanc T, et al. A landscape of germline mutations in a cohort of inherited bone marrow failure patients. Blood. 2018;131:717\u201332.","journal-title":"Blood"},{"issue":"6","key":"4552_CR5","doi-asserted-by":"publisher","first-page":"1052","DOI":"10.1007\/s10875-023-01545-0","volume":"43","author":"RA Voit","year":"2023","unstructured":"Voit RA, Sankaran VG. MECOM deficiency: from bone marrow failure to impaired B-cell development. J Clin Immunol. 2023;43(6):1052\u201366.","journal-title":"J Clin Immunol"},{"key":"4552_CR6","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1046\/j.1365-2141.2001.02834.x","volume":"113","author":"AA Thompson","year":"2001","unstructured":"Thompson AA, Woodruff K, Feig SA, et al. Congenital thrombocytopenia and radio ulnar synostosis: a new familial syndrome. Br J Haematol. 2001;113:866\u201370.","journal-title":"Br J Haematol"},{"issue":"6","key":"4552_CR7","doi-asserted-by":"publisher","first-page":"e26959","DOI":"10.1002\/pbc.26959","volume":"65","author":"T Osumi","year":"2018","unstructured":"Osumi T, Tsujimoto S, Nakabayashi K, et al. Somatic MECOM mosaicism in a patient with congenital bone marrow failure without a radial abnormality. Pediatr Blood Cancer. 2018;65(6):e26959.","journal-title":"Pediatr Blood Cancer"},{"issue":"5","key":"4552_CR8","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405\u201324.","journal-title":"Genet Med"},{"issue":"7","key":"4552_CR9","doi-asserted-by":"publisher","first-page":"1826","DOI":"10.1002\/ajmg.a.63208","volume":"191","author":"M Chinga","year":"2023","unstructured":"Chinga M, Bertuch A, Afify Z, et al. Am J Med Genet A. 2023;191(7):1826\u201335.","journal-title":"Am J Med Genet A"},{"issue":"1","key":"4552_CR10","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1097\/MCD.0000000000000200","volume":"27","author":"SV Lord","year":"2018","unstructured":"Lord SV, Jimenez JE, Kroeger ZA, et al. A MECOM variant in an African American child with radioulnar synostosis and thrombocytopenia. Clin Dysmorphol. 2018;27(1):9\u201311.","journal-title":"Clin Dysmorphol"},{"key":"4552_CR11","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.gene.2018.02.061","volume":"656","author":"E Kjeldsen","year":"2018","unstructured":"Kjeldsen E, Veigaard C, Aggerholm A, Hasle H. Congenital hypoplastic bone marrow failure associated with a de novo partial deletion of the MECOM gene at 3q26.2. Gene. 2018;656:86\u201394.","journal-title":"Gene"},{"issue":"2","key":"4552_CR12","doi-asserted-by":"publisher","first-page":"e55","DOI":"10.3324\/haematol.2017.178723","volume":"103","author":"T Ripperger","year":"2018","unstructured":"Ripperger T, Hofmann W, Koch JC, Steinemann D, et al. MDS1 and EVI1 complex locus (MECOM): a novel candidate gene for hereditary hematological malignancies. Haematologica. 2018;103(2):e55\u20138.","journal-title":"Haematologica"},{"issue":"4","key":"4552_CR13","doi-asserted-by":"publisher","first-page":"e27574","DOI":"10.1002\/pbc.27574","volume":"66","author":"A Loganathan","year":"2019","unstructured":"Loganathan A, Munirathnam D, Ravikumar T. A novel mutation in the MECOM gene causing radioulnar synostosis with amegakaryocytic thrombocytopenia (RUSAT-2) in an infant. Pediatr Blood Cancer. 2019;66(4):e27574.","journal-title":"Pediatr Blood Cancer"},{"issue":"2","key":"4552_CR14","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1002\/ajmg.a.37451","volume":"170A","author":"A Bouman","year":"2016","unstructured":"Bouman A, Knegt L, Gr\u00f6schel S, et al. Congenital thrombocytopenia in a neonate with an interstitial microdeletion of 3q26.2q26.31. Am J Med Genet A. 2016;170A(2):504\u20139.","journal-title":"Am J Med Genet A"},{"issue":"4","key":"4552_CR15","doi-asserted-by":"publisher","first-page":"e173","DOI":"10.3324\/haematol.2017.185033","volume":"103","author":"L Veken","year":"2018","unstructured":"Veken L, Maiburg M, Groenendaal F, et al. Lethal neonatal bone marrow failure syndrome with multiple congenital abnormalities, including limb defects, due to a constitutional deletion of 3\u2019 MECOM. Haematologica. 2018;103(4):e173\u20136.","journal-title":"Haematologica"},{"issue":"5","key":"4552_CR16","doi-asserted-by":"publisher","first-page":"e28215","DOI":"10.1002\/pbc.28215","volume":"67","author":"D Weizmann","year":"2020","unstructured":"Weizmann D, Pincez T, Roussy M, et al. New MECOM variant in a child with severe neonatal cytopenias spontaneously resolving. Pediatr Blood Cancer. 2020;67(5):e28215.","journal-title":"Pediatr Blood Cancer"},{"issue":"18","key":"4552_CR17","doi-asserted-by":"publisher","first-page":"5257","DOI":"10.1182\/bloodadvances.2020003812","volume":"6","author":"T Niihori","year":"2022","unstructured":"Niihori T, Tanoshim R, Sasahara Y, et al. Phenotypic heterogeneity in individuals with MECOM variants in 2 families. Blood Adv. 2022;6(18):5257\u201361.","journal-title":"Blood Adv"},{"issue":"4","key":"4552_CR18","doi-asserted-by":"publisher","first-page":"736","DOI":"10.24953\/turkjped.2021.4855","volume":"64","author":"B Delilo\u011flu","year":"2022","unstructured":"Delilo\u011flu B, T\u00fcfek\u00e7i \u00d6, T\u00fcz\u00fcn F, et al. A novel mecom gene mutation associated with amegakaryocytic thrombocytopenia in a premature infant. Turk J Pediatr. 2022;64(4):736\u201340.","journal-title":"Turk J Pediatr"},{"issue":"6","key":"4552_CR19","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1002\/pd.6353","volume":"43","author":"E Wall","year":"2023","unstructured":"Wall E, Forsyth J, Kinning E, et al. Fetal hydrops caused by a novel pathogenic MECOM variant. Prenat Diagn. 2023;43(6):717\u201320.","journal-title":"Prenat Diagn"},{"issue":"7","key":"4552_CR20","doi-asserted-by":"publisher","first-page":"e284","DOI":"10.3324\/haematol.2017.183855","volume":"103","author":"A Walne","year":"2018","unstructured":"Walne A, Tummala H, Ellison A, et al. Expanding the phenotypic and genetic spectrum of radioulnar synostosis associated hematological disease. Haematologica. 2018;103(7):e284\u20137.","journal-title":"Haematologica"},{"issue":"12","key":"4552_CR21","doi-asserted-by":"publisher","first-page":"e29761","DOI":"10.1002\/pbc.29761","volume":"69","author":"H Al-Abboh","year":"2022","unstructured":"Al-Abboh H, Zahra A, Adekile A. A novel MECOM variant associated with congenital amegakaryocytic thrombocytopenia and radioulnar synostosis. Pediatr Blood Cancer. 2022;69(12):e29761.","journal-title":"Pediatr Blood Cancer"},{"issue":"5","key":"4552_CR22","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1016\/j.gim.2022.01.021","volume":"24","author":"F Shen","year":"2022","unstructured":"Shen F, Yang Y, Zheng Y, et al. MECOM-related disorder: radioulnar synostosis without hematological aberration due to unique variants. Genet Med. 2022;24(5):1139\u201347.","journal-title":"Genet Med"},{"issue":"1","key":"4552_CR23","doi-asserted-by":"publisher","first-page":"53","DOI":"10.5045\/br.2021.2020299","volume":"56","author":"SS Datta","year":"2021","unstructured":"Datta SS, Basu S, Ghara N, et al. Utility of platelet cross-matching in a case of neonatal alloimmunue thrombocytopenia associated with a de novo MECOM variant. Blood Res. 2021;56(1):53\u20136.","journal-title":"Blood Res"},{"key":"4552_CR24","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1186\/s13104-015-1742-3","volume":"9","author":"E Cornet","year":"2016","unstructured":"Cornet E, Mossafa H, Courel K, et al. Persistent polyclonal binucleated B-cell lymphocytosis and MECOM gene amplification. BMC Res Notes. 2016;9:138.","journal-title":"BMC Res Notes"},{"key":"4552_CR25","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1182\/asheducation-2017.1.385","volume":"1","author":"P Noris","year":"2017","unstructured":"Noris P, Pecci A. Hereditary thrombocytopenias: a growing list of disorders. Hematol Am Soc Hematol Educ Program. 2017;1:385\u201399.","journal-title":"Hematol Am Soc Hematol Educ Program"},{"key":"4552_CR26","doi-asserted-by":"publisher","first-page":"e55","DOI":"10.3324\/haematol.2017.178723","volume":"103","author":"T Ripperger","year":"2018","unstructured":"Ripperger T, Hofmann W, Koch JC, et al. MDS1 and EVI1 complex locus(MECOM): a novel candidate gene for hereditary hematological malignancies. Haematologica. 2018;103:e55\u20138.","journal-title":"Haematologica"}],"container-title":["BMC Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12887-024-04552-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12887-024-04552-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12887-024-04552-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,20]],"date-time":"2024-01-20T05:03:51Z","timestamp":1705727031000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcpediatr.biomedcentral.com\/articles\/10.1186\/s12887-024-04552-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,20]]},"references-count":26,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["4552"],"URL":"https:\/\/doi.org\/10.1186\/s12887-024-04552-1","relation":{},"ISSN":["1471-2431"],"issn-type":[{"value":"1471-2431","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,20]]},"assertion":[{"value":"4 September 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 January 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 January 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Written informed consent was obtained from the parents for the publication of any potentially identifiable images or data included in this article. The study was approved by the Ethics Committee of West China Second University Hospital and complied with the guidelines outlined in the declaration of Helsinki were followed.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"N\/A.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publish"}},{"value":"The authors declare that there is no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"62"}}