{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T19:22:23Z","timestamp":1772997743123,"version":"3.50.1"},"reference-count":21,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000921","name":"European Cooperation in Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000921","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J Lab Hematology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Accurate classification of novel globin gene variants is critical for the diagnosis and management of thalassaemia. The adaptation of ACMG\/AMP guidelines for globin genes represents an important step toward standardising variant interpretation and enhancing clinical utility in the field. This study reports the haematological and molecular characteristics of a novel \u03b12\u2010globin variant identified in a Malay family.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A Malay family from Taiping, Perak, Malaysia, with a history of \u03b1\u2010thalassaemia, was recruited for this study. The proband's phenotype was assessed through comprehensive haematological analysis and clinical evaluation. Known \u03b1\u2010thalassaemia deletions and non\u2010deletional mutations were screened using gap\u2010PCR and ARMS\u2010PCR. Sanger sequencing of the\n                      <jats:italic>HBA<\/jats:italic>\n                      genes was conducted to characterise the proband's genotype in detail.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A novel pathogenic\n                      <jats:italic>HBA2<\/jats:italic>\n                      variant was identified, expanding the known mutational spectrum of \u03b1\u2010thalassaemia. This variant introduces a premature stop codon, occurs in trans with a known pathogenic allele associated with a significant clinical phenotype, segregates with the disease in the family, and is absent from major population databases. Based on haematological data, molecular findings, in silico predictions, and protein modeling, the variant meets the ACMG\/AMP criteria for pathogenicity adapted for \u03b1\u2010globin genes. We have designated this variant Hb Taiping, named after the location of its discovery. Its accurate classification is vital for carrier screening, genetic counselling, and prenatal diagnosis, thereby supporting improved clinical management.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study identifies and characterises a novel \u03b1\u2010globin gene variant, Hb Taiping, in a Malay family with \u03b1\u2010thalassaemia. The discovery contributes to the growing body of pathogenic mutations linked to \u03b1\u2010thalassaemia and underscores the importance of precise variant classification for effective diagnosis, risk assessment, and genetic counselling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ijlh.70037","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T14:35:57Z","timestamp":1767710157000},"page":"458-465","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>ACMG<\/scp>\n                    \/\n                    <scp>AMP<\/scp>\n                    \u2010Based Variant Classification of a Novel\n                    <scp>\n                      <i>HBA2<\/i>\n                    <\/scp>\n                    Variant (\n                    <scp>\n                      <i>HBA2<\/i>\n                    <\/scp>\n                    : C.297del, Hb Taiping) in Compound Heterozygosity With Hb Adana (\n                    <scp>\n                      <i>HBA2<\/i>\n                    <\/scp>\n                    :C.\n                    <scp>179G<\/scp>\n                    &gt;A) Causing Non\u2010Deletional Hb H Disease"],"prefix":"10.1111","volume":"48","author":[{"given":"Norafiza Mohd","family":"Yasin","sequence":"first","affiliation":[{"name":"Haematology Unit, Cancer Research Centre (CaRC), Institute for Medical Research (IMR) National Institute for Health (NIH) Setia Alam  Setia Alam Selangor Malaysia"},{"name":"Department of Clinical Genetics\/GD Leiden University Medical Centre  Leiden the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suguna","family":"Somasundram","sequence":"additional","affiliation":[{"name":"Haematology Unit, Cancer Research Centre (CaRC), Institute for Medical Research (IMR) National Institute for Health (NIH) Setia Alam  Setia Alam Selangor Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syahzuwan","family":"Hassan","sequence":"additional","affiliation":[{"name":"Haematology Unit, Cancer Research Centre (CaRC), Institute for Medical Research (IMR) National Institute for Health (NIH) Setia Alam  Setia Alam Selangor Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4527-0704","authenticated-orcid":false,"given":"Nur Aisyah","family":"Aziz","sequence":"additional","affiliation":[{"name":"Haematology Unit, Cancer Research Centre (CaRC), Institute for Medical Research (IMR) National Institute for Health (NIH) Setia Alam  Setia Alam Selangor Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faidatul Syazlin Abdul","family":"Hamid","sequence":"additional","affiliation":[{"name":"Haematology Unit, Cancer Research Centre (CaRC), Institute for Medical Research (IMR) National Institute for Health (NIH) Setia Alam  Setia Alam Selangor Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ezzanie Suffya","family":"Zulkefli","sequence":"additional","affiliation":[{"name":"Haematology Unit, Cancer Research Centre (CaRC), Institute for Medical Research (IMR) National Institute for Health (NIH) Setia Alam  Setia Alam Selangor Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nor Nazuha","family":"Mohamad","sequence":"additional","affiliation":[{"name":"Haematology Unit, Pathology Department Hospital Taiping  Taiping Perak Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chin Ming","family":"Lee","sequence":"additional","affiliation":[{"name":"Paediatric Unit, Department of Medicine Hospital Taiping  Taiping Perak Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohd Nazif","family":"Darawi","sequence":"additional","affiliation":[{"name":"Department of Medical Diagnostics, Faculty of Health Sciences University Selangor  Shah Alam Selangor Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thessalia","family":"Papasavva","sequence":"additional","affiliation":[{"name":"Molecular Genetics Thalassaemia Department Cyprus Institute of Neurology and Genetics  Nicosia Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Coralea","family":"Stephanou","sequence":"additional","affiliation":[{"name":"Molecular Genetics Thalassaemia Department Cyprus Institute of Neurology and Genetics  Nicosia Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petros","family":"Kountouris","sequence":"additional","affiliation":[{"name":"Molecular Genetics Thalassaemia Department Cyprus Institute of Neurology and Genetics  Nicosia Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra J. 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