{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T16:52:44Z","timestamp":1788281564605,"version":"build-2803163510"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,1,14]],"date-time":"2023-01-14T00:00:00Z","timestamp":1673654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["7\/1\/14\/2018\u2010RMC\/Nano\/BMS"],"award-info":[{"award-number":["7\/1\/14\/2018\u2010RMC\/Nano\/BMS"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Thalassemias are common monogenic autosomal recessive hemoglobin disorders. The usually asymptomatic heterozygotes (\u03b2\u2010thalassemia traits, \u03b2TT) may rarely develop non\u2010transfusion\u2010dependent\u2010thalassemia (NTDT) due to co\u2010inheritance of supernumerary \u03b1\u2010globin genes. Literature on phenotypic\/genotypic features of these rare combinations is limited.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>We studied the demographic, clinical, and laboratory data from 47 persons with co\u2010inherited \u03b2TT\u2009+\u2009supernumerary \u03b1\u2010globin genes. <jats:italic>HBB<\/jats:italic> mutations were tested for by ARMS\u2010PCR and\/or Sanger sequencing, \u03b1\u03b1\u03b1<jats:sup>(anti3.7)<\/jats:sup>\/\u03b1\u03b1\u03b1<jats:sup>(anti4.2)<\/jats:sup> and deletional \u03b1\u2010thalassemia testing by multiplex gap\u2010PCRs, and Xmn1<jats:sup>G<\/jats:sup>\u03b3 genotyping by PCR\u2010RFLP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The 47 cases comprised 0.08% of 61\u2009010 hemoglobinopathy screenings during the study period. Mean age was 31.9\u00a0\u00b1\u200914.7\u2009years (range 5.5\u201383\u2009years), with 57.4% males. Thirty (63.8%) had NTDT\u2010phenotype, 16 (34%) were asymptomatic\/minimally symptomatic, and 1 became transfusion\u2010dependent at the age of 20\u2009years. Anemia\/pallor and jaundice were the commonest complaints (76% each); 40% had required blood transfusions. Twenty\u2010one had splenomegaly, 14 had hepatomegaly. Mean hemoglobin was 9.0\u00a0\u00b1\u20091.9\u00a0g\/dl (range 4.0\u201313.0). HbA2 was 5.1\u00a0\u00b1\u20090.7% (3.4%\u20136.3%) and HbF% 4.2\u00a0\u00b1\u20093.2% (0.5%\u201318.4%). Forty\u2010four (93.6%) had \u03b1\u03b1\u03b1<jats:sup>anti3.7<\/jats:sup>, while 3 (6.4%) had \u03b1\u03b1\u03b1<jats:sup>anti4.2<\/jats:sup> triplications. <jats:italic>HBB<\/jats:italic>:c.92+5G&gt;C (47%), <jats:italic>HBB<\/jats:italic>:c.27_28insG (14.9%), and <jats:italic>HBB<\/jats:italic>:c.47G&gt;A (8.5%) were the commonest \u03b2\u2010globin mutations. One case showed <jats:italic>HBB<\/jats:italic>:c.\u2010138C&gt;T (\u03b2<jats:sup>++<\/jats:sup>), while the rest had \u03b2<jats:sup>0<\/jats:sup> or severe\u2010\u03b2<jats:sup>+<\/jats:sup> mutations. Symptomatic cases had significantly lower hemoglobins and higher HbF% than asymptomatic ones.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This largest Indian and globally second\u2010largest study reports the \u03b2TT\u2009+\u2009\u03b1\u03b1\u03b1<jats:sup>4.2<\/jats:sup> state for the first time in such genotypically\u2010complex Indian cases. Supernumerary \u03b1\u2010genes should be suspected in all \u03b2TT with disproportionate clinical symptoms, mild\u2010to\u2010moderately elevated HbF, and unexplained anisopoikilocytosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ejh.13923","type":"journal-article","created":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T15:13:03Z","timestamp":1672845183000},"page":"510-517","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Hematological and genetic profiles of persons with co\u2010inherited heterozygous \u03b2\u2010thalassemia and supernumerary \u03b1\u2010globin genes"],"prefix":"10.1111","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3429-4284","authenticated-orcid":false,"given":"Durga Devi","family":"Sundaresan","sequence":"first","affiliation":[{"name":"Hematology Department Postgraduate Institute of Medical Education &amp; Research (PGIMER)  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasbir Kaur","family":"Hira","sequence":"additional","affiliation":[{"name":"Hematology Department Postgraduate Institute of Medical Education &amp; Research (PGIMER)  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjeev","family":"Chhabra","sequence":"additional","affiliation":[{"name":"Hematology Department Postgraduate Institute of Medical Education &amp; Research (PGIMER)  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9071-7651","authenticated-orcid":false,"given":"Amita","family":"Trehan","sequence":"additional","affiliation":[{"name":"Pediatric Hematology\/Oncology Unit, Pediatrics Department Postgraduate Institute of Medical Education &amp; Research (PGIMER)  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4360-9348","authenticated-orcid":false,"given":"Alka Rani","family":"Khadwal","sequence":"additional","affiliation":[{"name":"Clinical Hematology and Medical Oncology Department Postgraduate Institute of Medical Education &amp; Research (PGIMER)  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1198-8491","authenticated-orcid":false,"given":"Pankaj","family":"Malhotra","sequence":"additional","affiliation":[{"name":"Clinical Hematology and Medical Oncology Department Postgraduate Institute of Medical Education &amp; Research (PGIMER)  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4741-3403","authenticated-orcid":false,"given":"Prashant","family":"Sharma","sequence":"additional","affiliation":[{"name":"Hematology Department Postgraduate Institute of Medical Education &amp; Research (PGIMER)  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8938-5423","authenticated-orcid":false,"given":"Reena","family":"Das","sequence":"additional","affiliation":[{"name":"Hematology Department Postgraduate Institute of Medical Education &amp; Research (PGIMER)  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,1,14]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781119579977"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-08-300335"},{"key":"e_1_2_11_4_1","volume-title":"Thalassemia \u2013 From Genotype to Phenotype [Internet]. 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