{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T13:55:24Z","timestamp":1792418124295,"version":"4.4.0"},"reference-count":17,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,2,17]],"date-time":"2021-02-17T00:00:00Z","timestamp":1613520000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Homozygous or compound heterozygous pathogenic variants in the <jats:italic>thromboxane A synthase 1<\/jats:italic> (<jats:italic>TBXAS1<\/jats:italic>) gene are associated with Ghosal hematodiaphyseal dysplasia (GHDD) which is characterized by defective hematopoiesis and increased bone density of long bones.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients 1 and 2 are identical twins, who presented with red blood cell transfusion\u2010dependent normocytic anemia and thrombocytopenia with bone marrow fibrosis and cortical bone thickening of long bones on plain radiograph. To clarify the etiology of their anemia and thrombocytopenia, whole blood was used for the DNA extraction and analyzed using next\u2010generation sequencing (NGS) on an in\u2010house bone marrow failure syndrome panel.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The NGS results indicated that these two patients carried two heterozygous variants in <jats:italic>TBXAS1<\/jats:italic>, exon7, c.583_584del, p.Ala195Leufs*12, and exon12, c.1420G&gt;T, p.Gly474Trp, which were inherited from their mother and father, respectively. Patients 1 and 2 have been on chronic oral steroids with normalization of hemoglobin and platelet count after steroid initiation. Patient 3 is their sister who has normal blood counts but also has the same variants in <jats:italic>TBXAS1<\/jats:italic> as her brothers. Radiographs showed cortical bone thickening and she has not required any treatment or transfusion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We report three Caucasian siblings from non\u2010consanguineous parents with novel compound heterozygous variants of <jats:italic>TBXAS1<\/jats:italic> presenting with the phenotypes of GHDD. These three cases illustrate the variable clinical expressivity of the GHDD from two\u2010compound heterozygous pathogenic variants of <jats:italic>TBXAS1<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1494","type":"journal-article","created":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T03:46:56Z","timestamp":1613620016000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Novel compound heterozygous variants of <i>TBXAS1<\/i> presenting with Ghosal hematodiaphyseal dysplasia treated with steroids"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0036-837X","authenticated-orcid":false,"given":"Sun Young","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pediatrics Division of Hematology\/Oncology\/Stem Cell Transplant Ann and Robert H. Lurie Children's Hospital of Chicago Northwestern University Feinberg School of Medicine Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Ing","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Laboratory Medicine Ann and Robert H. Lurie Children\u2019s Hospital of Chicago Northwestern University Feinberg School of Medicine Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunyou","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Laboratory Medicine Ann and Robert H. Lurie Children\u2019s Hospital of Chicago Northwestern University Feinberg School of Medicine Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai Lee","family":"Yap","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Laboratory Medicine Ann and Robert H. Lurie Children\u2019s Hospital of Chicago Northwestern University Feinberg School of Medicine Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rukhmi","family":"Bhat","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Hematology\/Oncology\/Stem Cell Transplant Ann and Robert H. Lurie Children's Hospital of Chicago Northwestern University Feinberg School of Medicine Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00256-014-1989-0"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2165"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transci.2019.04.027"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1684\/bdc.2011.1398"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12098-012-0872-z"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867043365260"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2007.66"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(88)80527-4"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13312-016-0851-y"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0000000000000279"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.228729"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4076"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.22662"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1994.00273.x"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12098-014-1654-6"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.26777"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1494","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.1494","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1494","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T18:15:21Z","timestamp":1693332921000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.1494"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,17]]},"references-count":17,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,3]]}},"alternative-id":["10.1002\/mgg3.1494"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.1494","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,17]]},"assertion":[{"value":"2020-02-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1494"}}