{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T12:16:49Z","timestamp":1791375409100,"version":"4.3.1"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T00:00:00Z","timestamp":1635120000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>In \u03b2\u2010thalassaemia, the severity of inherited \u03b2\u2010globin gene mutations determines the severity of the clinical phenotype at presentation and subsequent transfusion requirements. However, data on associated long\u2010term outcomes remain limited. We analysed data from 2109 \u03b2\u2010thalassaemia patients with available genotypes in a global database. Genotype severity was grouped as \u03b2<jats:sup>0<\/jats:sup>\/\u03b2<jats:sup>0<\/jats:sup>, \u03b2<jats:sup>0<\/jats:sup>\/\u03b2<jats:sup>+<\/jats:sup>, \u03b2<jats:sup>+<\/jats:sup>\/\u03b2<jats:sup>+<\/jats:sup>, \u03b2<jats:sup>0<\/jats:sup>\/\u03b2<jats:sup>++<\/jats:sup>, \u03b2<jats:sup>+<\/jats:sup>\/\u03b2<jats:sup>++<\/jats:sup>, and \u03b2<jats:sup>++<\/jats:sup>\/\u03b2<jats:sup>++<\/jats:sup>. Patients were followed from birth until death or loss to follow\u2010up. The median follow\u2010up time was 34\u00b71\u00a0years. Mortality and multiple morbidity outcomes were analyzed through five different stratification models of genotype severity groups. Interestingly, \u03b2<jats:sup>0<\/jats:sup> and \u03b2<jats:sup>+<\/jats:sup> mutations showed similar risk profiles. Upon adjustment for demographics and receipt of conventional therapy, patients with \u03b2<jats:sup>0<\/jats:sup>\/\u03b2<jats:sup>0<\/jats:sup>, \u03b2<jats:sup>0<\/jats:sup>\/\u03b2<jats:sup>+<\/jats:sup>, or \u03b2<jats:sup>+<\/jats:sup>\/\u03b2<jats:sup>+<\/jats:sup> had a 2\u00b7104\u2010increased risk of death [95% confidence interval (CI): 1\u00b7176\u20133\u00b7763, <jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b7011] and 2\u00b7956\u2010increased odds of multiple morbidity (95% CI: 2\u00b7310\u20133\u00b7784, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b7001) compared to patients in lower genotype severity groups. Cumulative survival estimates by age 65\u00a0years were 36\u00b78% for this subgroup compared with 90\u00b72% for patients in lower genotype severity groups (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b7001). Our study identified mortality and morbidity risk estimates across various genotype severity groups in patients with \u03b2\u2010thalassaemia and suggests inclusion of both \u03b2<jats:sup>+<\/jats:sup> and \u03b2<jats:sup>0<\/jats:sup> mutations in strata of greatest severity.<\/jats:p>","DOI":"10.1111\/bjh.17897","type":"journal-article","created":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T03:13:48Z","timestamp":1635218028000},"page":"414-423","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Primary <i>HBB<\/i> gene mutation severity and long\u2010term outcomes in a global cohort of \u03b2\u2010thalassaemia"],"prefix":"10.1111","volume":"196","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3935-903X","authenticated-orcid":false,"given":"Khaled M.","family":"Musallam","sequence":"first","affiliation":[{"name":"Thalassemia Center Burjeel Medical City  Abu Dhabi United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1037-1767","authenticated-orcid":false,"given":"Angela","family":"Vitrano","sequence":"additional","affiliation":[{"name":"Campus of Haematology Franco and Piera Cutino AOOR Villa Sofia\u2010V. Cervello  Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2284-8585","authenticated-orcid":false,"given":"Antonella","family":"Meloni","sequence":"additional","affiliation":[{"name":"MRI Unit Fondazione G. Monasterio CNR\u2010Regione Toscana  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastiano","family":"Addario Pollina","sequence":"additional","affiliation":[{"name":"D.A.S.O.E Regione Siciliana  Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vito","family":"Di Marco","sequence":"additional","affiliation":[{"name":"Department of Promozione della Salute Materno Infantile Medicina Interna e Specialistica di Eccellenza (PROMISE) University of Palermo  Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saqib","family":"Hussain Ansari","sequence":"additional","affiliation":[{"name":"Department of Pediatric Haematology &amp; Molecular Medicine National Institute of Blood Diseases and Bone Marrow Transplantation  Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldo","family":"Filosa","sequence":"additional","affiliation":[{"name":"Rare Blood Cell Disease Unit \"Cardarelli\" Hospital  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7361-3308","authenticated-orcid":false,"given":"Paolo","family":"Ricchi","sequence":"additional","affiliation":[{"name":"Rare Blood Cell Disease Unit \"Cardarelli\" Hospital  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Ceci","sequence":"additional","affiliation":[{"name":"Fondazione per la Ricerca Farmacologica Gianni Benzi Onlus  Valenzano (BA) Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahina","family":"Daar","sequence":"additional","affiliation":[{"name":"Department of Haematology College of Medicine and Health Sciences Sultan Qaboos University  Muscat Sultanate of Oman"},{"name":"Wallenberg Research Centre Stellenbosch Institute for Advanced Study Stellenbosch University  Stellenbosch South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efthymia","family":"Vlachaki","sequence":"additional","affiliation":[{"name":"Thalassaemia Unit Ippokratio University Hospital  Thessaloniki Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia T.","family":"Singer","sequence":"additional","affiliation":[{"name":"Division of Hematology\u2010Oncology Department of Pediatrics University of California San Francisco UCSF Benioff Children's Hospital Oakland  Oakland CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaki A.","family":"Naserullah","sequence":"additional","affiliation":[{"name":"Dammam Maternity and Child Hospital  Dammam Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Pepe","sequence":"additional","affiliation":[{"name":"MRI Unit Fondazione G. Monasterio CNR\u2010Regione Toscana  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Scondotto","sequence":"additional","affiliation":[{"name":"D.A.S.O.E Regione Siciliana  Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Dardanoni","sequence":"additional","affiliation":[{"name":"D.A.S.O.E Regione Siciliana  Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8555-1001","authenticated-orcid":false,"given":"Mehran","family":"Karimi","sequence":"additional","affiliation":[{"name":"Haematology Research Center Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal","family":"El\u2010Beshlawy","sequence":"additional","affiliation":[{"name":"Department of Pediatric Haematology Faculty of Medicine Cairo University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud","family":"Hajipour","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology, Hepatology and Nutrition Research Center Research Institute for Children\u2019s Health Shahid Beheshti University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fedele","family":"Bonifazi","sequence":"additional","affiliation":[{"name":"Fondazione per la Ricerca Farmacologica Gianni Benzi Onlus  Valenzano (BA) Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliott","family":"Vichinsky","sequence":"additional","affiliation":[{"name":"Division of Hematology\u2010Oncology Department of Pediatrics University of California San Francisco UCSF Benioff Children's Hospital Oakland  Oakland CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8515-2238","authenticated-orcid":false,"given":"Ali T.","family":"Taher","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine American University of Beirut Medical Center  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay G.","family":"Sankaran","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology Boston Children's Hospital and Department of Pediatric Oncology Dana\u2010Farber Cancer Institute Harvard Medical School  Boston MA USA"},{"name":"Broad Institute of MIT and Harvard  Cambridge MA USA"},{"name":"Harvard Stem Cell Institute  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelio","family":"Maggio","sequence":"additional","affiliation":[{"name":"Campus of Haematology Franco and Piera Cutino AOOR Villa Sofia\u2010V. 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