{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:57:11Z","timestamp":1753869431934,"version":"3.41.2"},"reference-count":6,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T00:00:00Z","timestamp":1747612800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["eJHaem"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>X\u2010linked sideroblastic anaemia (XLSA) is a rare hereditary disorder caused by mutations in the <jats:italic>ALAS2<\/jats:italic> gene, essential for haem biosynthesis. We report two male siblings, the first of whom developed severe microcytic hypochromic anaemia requiring regular transfusions, iron chelation and an allogeneic bone marrow transplant, while his brother displayed only mild microcytic hypochromic indices without anaemia. Initial genetic screening did not identify a pathogenic variant. However, duo exome sequencing later revealed an intronic <jats:italic>ALAS2<\/jats:italic> mutation, initially categorised as of uncertain significance and subsequently reclassified as pathogenic. This case underscores the diagnostic challenges posed by intronic mutations and the highly variable expressivity of XLSA, even among siblings.<\/jats:p><jats:p><jats:bold>Trial Registration<\/jats:bold>: The authors have confirmed clinical trial registration is not needed for this submission.<\/jats:p>","DOI":"10.1002\/jha2.70060","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T11:21:27Z","timestamp":1747653687000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["X\u2010Linked Sideroblastic Anaemia Caused by Intronic <i>ALAS2<\/i> Variant Resulting in Highly Variable Expressive Phenotype in Male Siblings, a Case Report"],"prefix":"10.1002","volume":"6","author":[{"given":"James","family":"O'Connor","sequence":"first","affiliation":[{"name":"School of Medicine Ulster University  Londonderry UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niall","family":"Mannion","sequence":"additional","affiliation":[{"name":"School of Medicine Ulster University  Londonderry UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caoimhe","family":"McKenna","sequence":"additional","affiliation":[{"name":"Northern Ireland Regional Genetics Laboratory  Belfast UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4570-9621","authenticated-orcid":false,"given":"Kerrie","family":"Sweeney","sequence":"additional","affiliation":[{"name":"Haematology department Antrim Area Hospital  Antrim UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9454-2692","authenticated-orcid":false,"given":"Aaron","family":"Niblock","sequence":"additional","affiliation":[{"name":"School of Medicine Ulster University  Londonderry UK"},{"name":"Haematology department Antrim Area Hospital  Antrim UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,5,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.2147\/JBM.S232644"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijlh.13214"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2018.08.008"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102018\u201008\u2010815951"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102002\u201003\u20100685"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.23616"}],"container-title":["eJHaem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jha2.70060","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T13:23:29Z","timestamp":1750685009000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jha2.70060"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,19]]},"references-count":6,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1002\/jha2.70060"],"URL":"https:\/\/doi.org\/10.1002\/jha2.70060","archive":["Portico"],"relation":{},"ISSN":["2688-6146","2688-6146"],"issn-type":[{"type":"print","value":"2688-6146"},{"type":"electronic","value":"2688-6146"}],"subject":[],"published":{"date-parts":[[2025,5,19]]},"assertion":[{"value":"2025-01-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70060"}}