{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T10:39:14Z","timestamp":1788863954363,"version":"build-2803163510"},"reference-count":35,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T00:00:00Z","timestamp":1683072000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004396","name":"Thailand Research Fund","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004396","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100017170","name":"Thailand Science Research and Innovation","doi-asserted-by":"crossref","award":["RTA6280005"],"award-info":[{"award-number":["RTA6280005"]}],"id":[{"id":"10.13039\/501100017170","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004704","name":"National Research Council of Thailand","doi-asserted-by":"crossref","award":["N42A650215"],"award-info":[{"award-number":["N42A650215"]}],"id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Mahasarakham University 2021","award":["6408066\/2564"],"award-info":[{"award-number":["6408066\/2564"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>\u03b2<\/jats:italic><jats:sup>0<\/jats:sup>-thalassemia deletion removing 5\u00b4<jats:italic>\u03b2<\/jats:italic>-globin promoter usually presents phenotype with high hemoglobin (Hb) A<jats:sub>2<\/jats:sub>and Hb F levels. We report the molecular characteristics and phenotype-genotype correlation in a large cohort of the<jats:italic>\u03b2<\/jats:italic><jats:sup>0<\/jats:sup>-thalassemia with 3.4 kb deletion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 148 subjects, including 127 heterozygotes, 20 Hb E-<jats:italic>\u03b2<\/jats:italic>-thalassemia patients, and a double heterozygote with<jats:italic>\u03b1<\/jats:italic>-globin gene triplication, were recruited. Hb and DNA analysis were performed to identify thalassemia mutations and four high Hb F single nucleotide polymorphisms (SNPs) including four base pair deletion (-AGCA) at<jats:sup>A<\/jats:sup><jats:italic>\u03b3<\/jats:italic>-globin promoter, rs5006884 on OR51B6 gene, \u2212158<jats:sup>G<\/jats:sup><jats:italic>\u03b3<\/jats:italic>-<jats:italic>Xmn<\/jats:italic>I, BCL11A binding motifs (TGGTCA) between 3\u00b4<jats:sup>A<\/jats:sup><jats:italic>\u03b3<\/jats:italic>-globin gene and 5\u00b4<jats:italic>\u03b4<\/jats:italic>-globin gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>It was found that heterozygous<jats:italic>\u03b2<\/jats:italic><jats:sup>0<\/jats:sup>-thalassemia and Hb E-<jats:italic>\u03b2<\/jats:italic><jats:sup>0<\/jats:sup>-thalassemia with 3.4 kb deletion had significantly higher Hb, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and Hb<jats:italic>F<\/jats:italic>values as compared with those with other mutations. Co-inheritance of heterozygous<jats:italic>\u03b2<\/jats:italic><jats:sup>0<\/jats:sup>-thalassemia with 3.4 kb deletion and<jats:italic>\u03b1<\/jats:italic>-thalassemia was associated with even higher MCV and MCH values. The Hb E-<jats:italic>\u03b2<\/jats:italic><jats:sup>0<\/jats:sup>-thalassemia patients carried a non-transfusion-dependent thalassemia phenotype with an average Hb of around 10 g\/dL without blood transfusion. A hitherto undescribed double heterozygous<jats:italic>\u03b2<\/jats:italic><jats:sup>0<\/jats:sup>-thalassemia with 3.4 kb deletion and<jats:italic>\u03b1<\/jats:italic>-globin gene triplication presented as a plain<jats:italic>\u03b2<\/jats:italic>-thalassemia trait. Most of the subjects had wild-type sequences for the four high Hb F SNPs examined. No significant difference in Hb F was observed between those of subjects with and without these SNPs. Removal of the 5\u00b4<jats:italic>\u03b2<\/jats:italic>-globin promoter may likely be responsible for this unusual phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results indicate that<jats:italic>\u03b2<\/jats:italic><jats:sup>0<\/jats:sup>-thalassemia with 3.4 kb deletion is a mild<jats:italic>\u03b2<\/jats:italic>-thalassemia allele. This information should be provided at genetic counseling and prenatal thalassemia diagnosis.<\/jats:p><\/jats:sec>","DOI":"10.7717\/peerj.15308","type":"journal-article","created":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T07:21:27Z","timestamp":1683098487000},"page":"e15308","source":"Crossref","is-referenced-by-count":6,"title":["Molecular basis of a high Hb A<sub>2<\/sub>\/Hb F<i>\u03b2<\/i>-thalassemia trait: a retrospective analysis, genotype-phenotype interaction, diagnostic implication, and identification of a novel interaction with<i>\u03b1<\/i>-globin gene triplication"],"prefix":"10.7717","volume":"11","author":[{"given":"Chayada","family":"Soontornpanawet","sequence":"first","affiliation":[{"name":"Centre for Research & Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Muang, Khon Kaen, 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