{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T18:12:46Z","timestamp":1778782366145,"version":"3.51.4"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>This study aimed to characterize the molecular and hematologic features of hemoglobin (Hb) Hekinan II in northern Thailand and to evaluate its phenotypic expression when co-inherited with other hemoglobinopathies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In total, 2314 blood samples were drawn for routine Hb analysis using high-performance liquid chromatography and capillary electrophoresis, and common \u03b10-thalassemia deletions were detected by multiplex real-time polymerase chain reaction with high-resolution melting analysis. Targeted next-generation sequencing using DNA nanoball sequencing technology was applied to identify variations in the HBA1, HBA2, and HBB genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Routine laboratory screening failed to detect Hb Hekinan II in all cases. Molecular analysis identified 13 (0.6%) carriers. Individuals with heterozygous Hb Hekinan II showed normal Hb profiles and near-normal red blood cell indices, confirming its clinically silent nature. Co-inheritance with HbE resulted in mild microcytosis resembling the HbE trait, while more complex genotypes involving \u03b20-thalassemia, \u03b1+-thalassemia, or additional \u03b1-globin variants produced variable hematologic phenotypes. All cases were detected only by molecular methods and were missed by conventional Hb typing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Hemoglobin Hekinan II is a clinically benign but diagnostically challenging \u03b1-globin variant that cannot be reliably identified by routine screening. Integrating targeted molecular diagnostics is essential for accurate detection and genetic counseling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/labmed\/lmag028","type":"journal-article","created":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T11:14:20Z","timestamp":1776510860000},"source":"Crossref","is-referenced-by-count":0,"title":["Hemoglobin Hekinan II (\n                    <i>HBA1<\/i>\n                    :c.84G&amp;gt;T): an electrophoretically silent \u03b1-globin variant missed by routine screening in northern Thailand"],"prefix":"10.1093","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7946-1515","authenticated-orcid":false,"given":"Moe","family":"Theingi","sequence":"first","affiliation":[{"name":"Division of Clinical Microscopy, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University , Chiang Mai,","place":["Thailand"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chedtapak","family":"Ruengdit","sequence":"additional","affiliation":[{"name":"Associated Medical Sciences Clinical Service Center, Faculty of Associated Medical Sciences, Chiang Mai University , Chiang Mai,","place":["Thailand"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manoo","family":"Punyamung","sequence":"additional","affiliation":[{"name":"Associated Medical Sciences Clinical Service Center, Faculty of Associated Medical Sciences, Chiang Mai University , Chiang Mai,","place":["Thailand"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sakorn","family":"Pornprasert","sequence":"additional","affiliation":[{"name":"Division of Clinical Microscopy, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University , Chiang Mai,","place":["Thailand"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"2026051413323202500_lmag028-B1","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1111\/j.1749-6632.1980.tb33674.x","article-title":"Thalassemia in Thailand","volume":"344","author":"Wasi","year":"1980","journal-title":"Ann N Y Acad Sci"},{"key":"2026051413323202500_lmag028-B2","doi-asserted-by":"publisher","first-page":"61","DOI":"10.3109\/03630268808996883","article-title":"An electrophoretically silent hemoglobin variant, Hb Hekinan [alpha 27(B8)Glu----Asp] found in a Japanese","volume":"12","author":"Harano","year":"1988","journal-title":"Hemoglobin"},{"key":"2026051413323202500_lmag028-B3","doi-asserted-by":"publisher","first-page":"627","DOI":"10.3109\/03630269009046971","article-title":"Hb Hekinan observed in three Chinese from Macau; identification of the GAG----GAT mutation in the alpha 1-globin gene","volume":"14","author":"Zhao","year":"1990","journal-title":"Hemoglobin"},{"key":"2026051413323202500_lmag028-B4","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1007\/s12185-017-2186-4","article-title":"The first validated criteria for effective screening and a new simplified method for \u03b1-globin gene sequencing for diagnosis of uncommon \u03b1-globin mutations","volume":"105","author":"Uaprasert","year":"2017","journal-title":"Int J Hematol"},{"key":"2026051413323202500_lmag028-B5","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1089\/gtmb.2015.0182","article-title":"Hemoglobin variants in Northern Thailand: prevalence, heterogeneity and molecular characteristics","volume":"20","author":"Panyasai","year":"2016","journal-title":"Genet Test Mol Biomarkers"},{"key":"2026051413323202500_lmag028-B6","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1034\/j.1600-0609.2003.00049.x","article-title":"Complex interaction of Hb Hekinan [\u03b127(B8) Glu\u2013Asp] and Hb E [\u03b226(B8) Glu\u2013Lys] with a deletional \u03b1-thalassemia 1 in a Thai family","volume":"70","author":"Fucharoen","year":"2003","journal-title":"Eur J Haematol"},{"key":"2026051413323202500_lmag028-B7","doi-asserted-by":"publisher","first-page":"2456679","DOI":"10.1080\/16078454.2025.2456679","article-title":"Comprehensive hematological and molecular characterization of hemoglobin Hekinan [\u03b127(B8)Glu\u2192Asp(\u03b11), HBA1: c.84G\u2009&gt;\u2009T] in a large Thai cohort","volume":"30","author":"Suksusut","year":"2025","journal-title":"Hematology"},{"key":"2026051413323202500_lmag028-B8","doi-asserted-by":"publisher","first-page":"75","DOI":"10.3109\/03630269.2015.1113990","article-title":"Ten years of routine \u03b1- and \u03b2-globin gene sequencing in UK hemoglobinopathy referrals reveals 60 novel mutations","volume":"40","author":"Henderson","year":"2016","journal-title":"Hemoglobin"},{"key":"2026051413323202500_lmag028-B9","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1093\/labmed\/lmae023","article-title":"A clinical update of compound heterozygosity for hemoglobin Hekinan II [\u03b127(B8)Glu-Asp; HBA1: c.84G&gt;T] variant in China","volume":"55","author":"Pan","year":"2024","journal-title":"Lab Med"},{"key":"2026051413323202500_lmag028-B10","doi-asserted-by":"publisher","first-page":"2406620","DOI":"10.1080\/19932820.2024.2406620","article-title":"Interactions of electrophoretically silent hemoglobin Hekinan II [HBA1: c.84G&gt;T] with various forms of \u03b1-thalassemias and other hemoglobinopathies: novel insights into the molecular and hematological characteristics and genetic origins","volume":"19","author":"Panyasai","year":"2024","journal-title":"Libyan J Med"},{"key":"2026051413323202500_lmag028-B11","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1080\/03630269.2025.2534705","article-title":"Novel double heterozygosity: HBA2: c.70G\u2009&gt;\u2009A (Hb Chad)\/HBB: c.-78A\u2009&gt;\u2009G and novel compound heterozygosity: HBA2: c.70G\u2009&gt;\u2009A (Hb Chad)\/HBA1: c.84G\u2009&gt;\u2009T (Hb Hekinan II) hemoglobinopathy in a Chinese family","volume":"49","author":"Ye","year":"2025","journal-title":"Hemoglobin"},{"key":"2026051413323202500_lmag028-B12","first-page":"506","article-title":"Chelex 100 as a medium for simple extraction of DNA for PCR-based typing from forensic material","volume":"10","author":"Walsh","year":"1991","journal-title":"Biotechniques"},{"key":"2026051413323202500_lmag028-B13","doi-asserted-by":"publisher","first-page":"e0293838","DOI":"10.1371\/journal.pone.0293838","article-title":"Single-tube multiplex real-time PCR with EvaGreen and high-resolution melting analysis for diagnosis of \u03b10-thalassemia--SEA,--THAI, and--CR type deletions","volume":"18","author":"Ruengdit","year":"2023","journal-title":"PLoS One"},{"key":"2026051413323202500_lmag028-B14","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1038\/gim.2016.218","article-title":"Next-generation sequencing improves thalassemia carrier screening among premarital adults in a high prevalence population: the Dai nationality, China","volume":"19","author":"He","year":"2017","journal-title":"Genet Med"},{"key":"2026051413323202500_lmag028-B15","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1111\/ggi.13194","article-title":"Iron deficiency anemia in older adults: a review","volume":"18","author":"Joosten","year":"2018","journal-title":"Geriatr Gerontol Int"},{"key":"2026051413323202500_lmag028-B16","doi-asserted-by":"publisher","first-page":"373","DOI":"10.3390\/diagnostics13030373","article-title":"Next-generation sequencing (NGS) and third-generation sequencing (TGS) for the diagnosis of thalassemia","volume":"13","author":"Hassan","year":"2023","journal-title":"Diagnostics (Basel)"},{"key":"2026051413323202500_lmag028-B17","doi-asserted-by":"publisher","first-page":"571","DOI":"10.3109\/03630268108991688","article-title":"Hemoglobin A2 in hyperthyroidism","volume":"5","author":"Kendall","year":"1981","journal-title":"Hemoglobin"},{"key":"2026051413323202500_lmag028-B18","doi-asserted-by":"publisher","first-page":"4454","DOI":"10.1182\/blood-2011-04-345736","article-title":"KLF1 gene mutations cause borderline HbA(2)","volume":"118","author":"Perseu","year":"2011","journal-title":"Blood"},{"key":"2026051413323202500_lmag028-B19","doi-asserted-by":"publisher","first-page":"122","DOI":"10.3109\/23744235.2015.1089592","article-title":"Effect of antiretroviral therapy on hemoglobin A2 values can have implications in antenatal beta-thalassemia screening programs","volume":"48","author":"Bhagat","year":"2016","journal-title":"Infect Dis (Lond)"},{"key":"2026051413323202500_lmag028-B20","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1080\/03630260902813486","article-title":"Increased Hb A2 values in an HIV-1-infected patient receiving antiretroviral drugs: a pitfall for thalassemia antenatal diagnosis","volume":"33","author":"Pornprasert","year":"2009","journal-title":"Hemoglobin"},{"key":"2026051413323202500_lmag028-B21","doi-asserted-by":"publisher","first-page":"35","DOI":"10.2147\/jbm.S159295","article-title":"Genotype-phenotype correlation among beta-thalassemia and beta-thalassemia\/HbE disease in Thai children: predictable clinical spectrum using genotypic analysis","volume":"9","author":"Traivaree","year":"2018","journal-title":"J Blood Med"},{"key":"2026051413323202500_lmag028-B22","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1007\/s00277-003-0689-y","article-title":"Molecular and hematologic features of hemoglobin E heterozygotes with different forms of \u03b1-thalassemia in Thailand","volume":"82","author":"Sanchaisuriya","year":"2003","journal-title":"Ann Hematol"},{"key":"2026051413323202500_lmag028-B23","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1002\/j.1460-2075.1984.tb01853.x","article-title":"Molecular characterization of seven beta-thalassemia mutations in Asian Indians","volume":"3","author":"Kazazian","year":"1984","journal-title":"Embo J"},{"key":"2026051413323202500_lmag028-B24","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1097\/00043426-200011000-00026","article-title":"Genetic factors affecting clinical severity in beta-thalassemia syndromes","volume":"22","author":"Winichagoon","year":"2000","journal-title":"J Pediatr Hematol Oncol"},{"key":"2026051413323202500_lmag028-B25","doi-asserted-by":"publisher","first-page":"101165","DOI":"10.1016\/j.blre.2023.101165","article-title":"\u0391lpha-thalassemia: a practical overview","volume":"64","author":"Musallam","year":"2024","journal-title":"Blood Rev"},{"key":"2026051413323202500_lmag028-B26","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1080\/03630269.2020.1768109","article-title":"Hb Westmead (HBA2: c.369C&gt;G): hematological characteristics in heterozygotes with and without \u03b1(0)-thalassemia","volume":"44","author":"Jiang","year":"2020","journal-title":"Hemoglobin"}],"container-title":["Laboratory Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/labmed\/article-pdf\/57\/3\/lmag028\/68287378\/lmag028.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/labmed\/article-pdf\/57\/3\/lmag028\/68287378\/lmag028.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T17:32:37Z","timestamp":1778779957000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/labmed\/article\/doi\/10.1093\/labmed\/lmag028\/8678320"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,3]]},"references-count":26,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,4,3]]}},"URL":"https:\/\/doi.org\/10.1093\/labmed\/lmag028","relation":{},"ISSN":["0007-5027","1943-7730"],"issn-type":[{"value":"0007-5027","type":"print"},{"value":"1943-7730","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,5]]},"published":{"date-parts":[[2026,4,3]]},"article-number":"lmag028"}}