{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T20:26:19Z","timestamp":1789503979030,"version":"build-2803163510"},"reference-count":20,"publisher":"BMJ","issue":"1","funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI12\/01068"],"award-info":[{"award-number":["PI12\/01068"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2016,6,15]]},"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Haemoglobin A\n                      <jats:sub>2<\/jats:sub>\n                      (HbA\n                      <jats:sub>2<\/jats:sub>\n                      ) consists of two globin chains, \u03b1 and \u03b2. Alterations in any of these genes influences the level of HbA\n                      <jats:sub>2<\/jats:sub>\n                      . Here, we present cases of structural Hb variants and thalassaemias which present either alone or together and reduce the level of HbA\n                      <jats:sub>2<\/jats:sub>\n                      at varying degrees. Furthermore, we present a novel structural mutation in the \u03b4 globin gene, called Hb A\n                      <jats:sub>2<\/jats:sub>\n                      -Madrid.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The levels of HbA\n                      <jats:sub>2<\/jats:sub>\n                      and HbF and the different haemoglobin variants were measured and analysed by ion exchange high performance liquid chromatography (HPLC, VARIANT II), the types of haemoglobins were determined by capillary zone electrophoresis (CZE) (Sebia) and the globin chains were determined by reversed-phase HPLC. Genetic analysis was performed by automatic sequencing of the \u03b1 and \u03b4 genes as well as by multiple PCRs for the \u03b1 globin genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In \u03b1 thalassaemia (n=94), the HbA\n                      <jats:sub>2<\/jats:sub>\n                      levels ranged from 1.39% to 2.43%. Among individuals with \u03b4 thalassaemia (n=5), the HbA\n                      <jats:sub>2<\/jats:sub>\n                      level of those with \u03b4\n                      <jats:sup>+<\/jats:sup>\n                      thalassaemia was 1.77%, and that of those with \u03b4\n                      <jats:sup>0<\/jats:sup>\n                      thalassaemia was 1.70%. Among the individuals with \u03b4\u03b2 thalassaemia (n=13), those who were homozygous lacked HbA\n                      <jats:sub>2<\/jats:sub>\n                      . All structural haemoglobinopathies (n=97) were heterozygous; the \u03b1 chain variants (n=84) presented with an HbA\n                      <jats:sub>2<\/jats:sub>\n                      level of 1.76%, while the \u03b4 chain variants (n=13) presented with a level of 1.75%.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      HbA\n                      <jats:sub>2<\/jats:sub>\n                      is an essential parameter in the diagnostics of haemoglobinopathies. HPLC-EC and CZE allow the quantification of HbA\n                      <jats:sub>2<\/jats:sub>\n                      . Here, we show that quantification of HbA\n                      <jats:sub>2<\/jats:sub>\n                      is critical for the identification of \u03b1, \u03b4 and \u03b2\u03b4 thalassaemias. Structural variants are discovered by HPLC. Molecular genetics is required for the proper identification of the mutations. Only with this knowledge is genetic counselling possible.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jclinpath-2016-203879","type":"journal-article","created":{"date-parts":[[2016,7,7]],"date-time":"2016-07-07T23:49:04Z","timestamp":1467935344000},"page":"75-80","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Haemoglobinopathies that occur with decreased HbA\n                    <sub>2<\/sub>\n                    levels: a gene mutation set involving the \u03b4 gene at a Spanish centre"],"prefix":"10.1136","volume":"70","author":[{"given":"Ana","family":"Villegas","sequence":"first","affiliation":[{"name":"Servicio de Hematolog\u00eda y Hemoterapia, Hospital Cl\u00ednico San Carlos, IdISS, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando Ata\u00falfo","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Servicio de Hematolog\u00eda y Hemoterapia, Hospital Cl\u00ednico San Carlos, IdISS, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge M","family":"Nieto","sequence":"additional","affiliation":[{"name":"Servicio de Hematolog\u00eda y Hemoterapia, Hospital Cl\u00ednico San Carlos, IdISS, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e9lix","family":"de la Fuente-Gonzalo","sequence":"additional","affiliation":[{"name":"Servicio de Hematolog\u00eda y Hemoterapia, Hospital Cl\u00ednico San Carlos, IdISS, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Servicio de Hematolog\u00eda y Hemoterapia, Hospital Cl\u00ednico San Carlos, IdISS, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Josefa","family":"Torrej\u00f3n","sequence":"additional","affiliation":[{"name":"Servicio de An\u00e1lisis Cl\u00ednicos, Hospital Cl\u00ednico San Carlos, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paloma","family":"Ropero","sequence":"additional","affiliation":[{"name":"Servicio de Hematolog\u00eda y Hemoterapia, Hospital Cl\u00ednico San Carlos, IdISS, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2016,7,7]]},"reference":[{"key":"2025120518084791000_70.1.75.1","unstructured":"Telen MJ . 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Hemoglobin A2 lowered by iron deficiency and \u03b1-thalassemia: should screening recommendation for \u03b2-thalassemia change?. Hindawi Publishing Corporation ISRN Hematology Volume, 2013. 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