{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T21:59:49Z","timestamp":1780437589058,"version":"3.54.1"},"reference-count":32,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T00:00:00Z","timestamp":1681689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RC2 DK122533"],"award-info":[{"award-number":["RC2 DK122533"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The <jats:italic>MECOM<\/jats:italic> gene encodes multiple protein isoforms that are essential for hematopoietic stem cell self\u2010renewal and maintenance. Germline <jats:italic>MECOM<\/jats:italic> variants have been associated with congenital thrombocytopenia, radioulnar synostosis and bone marrow failure; however, the phenotypic spectrum of <jats:italic>MECOM<\/jats:italic>\u2010associated syndromes continues to expand and novel pathogenic variants continue to be identified. We describe eight unrelated patients who add to the previously known phenotypes and genetic defects of <jats:italic>MECOM<\/jats:italic>\u2010associated syndromes. As each subject presented with unique <jats:italic>MECOM<\/jats:italic> variants, the series failed to demonstrate clear genotype\u2010to\u2010phenotype correlation but may suggest a role for additional modifiers that affect gene expression and subsequent phenotype. Recognition of the expanded hematologic and non\u2010hematologic clinical features allows for rapid molecular diagnosis, early identification of life\u2010threatening complications, and improved genetic counseling for families. A centralized international publicly accessible database to share annotated <jats:italic>MECOM<\/jats:italic> variants would advance their clinical interpretation and provide a foundation to perform functional <jats:italic>MECOM<\/jats:italic> studies.<\/jats:p>","DOI":"10.1002\/ajmg.a.63208","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T11:52:33Z","timestamp":1681732353000},"page":"1826-1835","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Expanded phenotypic and hematologic abnormalities beyond bone marrow failure in <i>MECOM<\/i>\u2010associated syndromes"],"prefix":"10.1002","volume":"191","author":[{"given":"Michell M.","family":"Lozano Chinga","sequence":"first","affiliation":[{"name":"Primary Children's Hospital University of Utah  Salt Lake City Utah USA"},{"name":"University of Iowa Hospitals and Clinics  Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison A.","family":"Bertuch","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine and Texas Children's Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeinab","family":"Afify","sequence":"additional","affiliation":[{"name":"Primary Children's Hospital University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaylee","family":"Dollerschell","sequence":"additional","affiliation":[{"name":"Children's Hospital Colorado University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne I.","family":"Hsu","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine and Texas Children's Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tami D.","family":"John","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine and Texas Children's Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily S.","family":"Rao","sequence":"additional","affiliation":[{"name":"Johns Hopkins Hospital  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert Grant","family":"Rowe","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber\/Boston Children's Cancer and Blood Disorders Center, Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay G.","family":"Sankaran","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber\/Boston Children's Cancer and Blood Disorders Center, Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4683-9958","authenticated-orcid":false,"given":"Akiko","family":"Shimamura","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber\/Boston Children's Cancer and Blood Disorders Center, Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Williams","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber\/Boston Children's Cancer and Blood Disorders Center, Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0389-2297","authenticated-orcid":false,"given":"Taizo A.","family":"Nakano","sequence":"additional","affiliation":[{"name":"Children's Hospital Colorado University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.29761"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/426952"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-09-806489"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37451"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1079-9796(03)00159-1"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1989.tb04267.x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3121\/cmr.4.1.66"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018016501"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-2725(99)00064-3"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2010.04.007"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2012.02303.x"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2018.02.061"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-0175"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/27945"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12092667"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCD.0000000000000200"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2012-100990"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.10.010"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020003812"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.26959"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.111.2.479"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.178723"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2017.04.004"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2022.01.021"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2088"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/82511"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.185033"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1101\/2021.12.09.471942"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.183855"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.214221"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-02-334680"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63208","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T02:50:06Z","timestamp":1722394206000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63208"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,17]]},"references-count":32,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["10.1002\/ajmg.a.63208"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63208","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,17]]},"assertion":[{"value":"2022-01-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}