The Clinical and Laboratory Profiles of a Deletional α2-Globin Gene Polyadenylation Signal Sequence (AATAAA > AATA--) [HBA2:c.*93_*94delAA]: The Malaysian Experience
Poly A (AATAAA > AATA--) [HBA2:c.*93_*94delAA] is a rare α-variant reported in our population. It is caused by 2 bp deletion (--AA) in the α2 poly A sequence, leading to a significant α–thalassaemia phenotype. <b>Background/Objectives</b>: This study describes the haematological param...
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2025-05-01
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| author | Norafiza Mohd Yasin Syahzuwan Hassan Nur Aisyah Aziz Faidatul Syazlin Abdul Hamid Ezalia Esa Ezzanie Suffya Zulkefli Rohana Ghazali Syirah Nazirah Tajuddin Mohd Nazif Darawi Yuslina Mat Yusoff Cornelis L. Harteveld |
| author_facet | Norafiza Mohd Yasin Syahzuwan Hassan Nur Aisyah Aziz Faidatul Syazlin Abdul Hamid Ezalia Esa Ezzanie Suffya Zulkefli Rohana Ghazali Syirah Nazirah Tajuddin Mohd Nazif Darawi Yuslina Mat Yusoff Cornelis L. Harteveld |
| author_sort | Norafiza Mohd Yasin |
| collection | DOAJ |
| description | Poly A (AATAAA > AATA--) [HBA2:c.*93_*94delAA] is a rare α-variant reported in our population. It is caused by 2 bp deletion (--AA) in the α2 poly A sequence, leading to a significant α–thalassaemia phenotype. <b>Background/Objectives</b>: This study describes the haematological parameters, phenotype, and genotype characteristics of AATA(--AA) in the Malaysian population. <b>Methods</b>: The study was carried out on 17 177 cases referred to the Institute for Medical Research, Malaysia, for further diagnosis of α-thalassaemia in a five-year period. Alpha-Gap and ARMS-PCR were performed to detect common α-thalassaemia, followed by <i>HBA1</i> and <i>HBA2</i> genes sequencing and multiplex ligation-dependent probe amplification (MLPA). Haematological parameters among various groups with the AATA(--AA) allele were presented in this study. <b>Results</b>: Thirty-two patients with AATA(--AA) displaying an α–thalassaemia-like phenotype were analysed. They comprised 22 (68.75%) AATA(--AA) carriers, 2 (6.25%) compounds with 3.7 deletion, 2 (6.25%) compounds with --SEA deletion, 1 (3.12%) AATA(--AA) homozygote, and 3 (9.37%) compounds of Hb Adana, Hb CS, and Hb Pakse with co-inheritance Hb E, respectively. Most of the patients with AATA(--AA) compounds with the α-variant exhibited a significant phenotype between moderate to severe thalassaemia, especially cases with compound α<sup>−AA</sup>α/α<sup>Adana</sup>α. <b>Conclusions</b>: AATA(--AA) is a significant pathogenic variant that should be diagnosed to prevent significant thalassaemia phenotype or transfusion-dependent thalassaemia. |
| format | Article |
| id | doaj-art-608ae78ef3d348748e972768ff1aaa4c |
| institution | OA Journals |
| issn | 2075-4418 |
| language | English |
| publishDate | 2025-05-01 |
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| spelling | doaj-art-608ae78ef3d348748e972768ff1aaa4c2025-08-20T01:56:31ZengMDPI AGDiagnostics2075-44182025-05-011510128410.3390/diagnostics15101284The Clinical and Laboratory Profiles of a Deletional α2-Globin Gene Polyadenylation Signal Sequence (AATAAA > AATA--) [HBA2:c.*93_*94delAA]: The Malaysian ExperienceNorafiza Mohd Yasin0Syahzuwan Hassan1Nur Aisyah Aziz2Faidatul Syazlin Abdul Hamid3Ezalia Esa4Ezzanie Suffya Zulkefli5Rohana Ghazali6Syirah Nazirah Tajuddin7Mohd Nazif Darawi8Yuslina Mat Yusoff9Cornelis L. Harteveld10Haematology Unit, Cancer Research Centre (CaRC), Institute for Medical Research (IMR), National Institute for Health (NIH), Shah Alam 40170, Selangor, MalaysiaHaematology Unit, Cancer Research Centre (CaRC), Institute for Medical Research (IMR), National Institute for Health (NIH), Shah Alam 40170, Selangor, MalaysiaHaematology Unit, Cancer Research Centre (CaRC), Institute for Medical Research (IMR), National Institute for Health (NIH), Shah Alam 40170, Selangor, MalaysiaHaematology Unit, Cancer Research Centre (CaRC), Institute for Medical Research (IMR), National Institute for Health (NIH), Shah Alam 40170, Selangor, MalaysiaHaematology Unit, Cancer Research Centre (CaRC), Institute for Medical Research (IMR), National Institute for Health (NIH), Shah Alam 40170, Selangor, MalaysiaHaematology Unit, Cancer Research Centre (CaRC), Institute for Medical Research (IMR), National Institute for Health (NIH), Shah Alam 40170, Selangor, MalaysiaHaematology Unit, Department of Pathology, Hospital Melaka, Melaka 75400, MalaysiaHaematology Unit, Department of Pathology, Hospital Tuanku Jaafar, Seremban 70300, Negeri Sembilan, MalaysiaDepartment of Medical Diagnostics, Faculty of Health Sciences, University Selangor, Shah Alam 40000, Selangor, MalaysiaHaematology Unit, Cancer Research Centre (CaRC), Institute for Medical Research (IMR), National Institute for Health (NIH), Shah Alam 40170, Selangor, MalaysiaLeiden University Medical Centre, 2333 ZA Leiden, The NetherlandsPoly A (AATAAA > AATA--) [HBA2:c.*93_*94delAA] is a rare α-variant reported in our population. It is caused by 2 bp deletion (--AA) in the α2 poly A sequence, leading to a significant α–thalassaemia phenotype. <b>Background/Objectives</b>: This study describes the haematological parameters, phenotype, and genotype characteristics of AATA(--AA) in the Malaysian population. <b>Methods</b>: The study was carried out on 17 177 cases referred to the Institute for Medical Research, Malaysia, for further diagnosis of α-thalassaemia in a five-year period. Alpha-Gap and ARMS-PCR were performed to detect common α-thalassaemia, followed by <i>HBA1</i> and <i>HBA2</i> genes sequencing and multiplex ligation-dependent probe amplification (MLPA). Haematological parameters among various groups with the AATA(--AA) allele were presented in this study. <b>Results</b>: Thirty-two patients with AATA(--AA) displaying an α–thalassaemia-like phenotype were analysed. They comprised 22 (68.75%) AATA(--AA) carriers, 2 (6.25%) compounds with 3.7 deletion, 2 (6.25%) compounds with --SEA deletion, 1 (3.12%) AATA(--AA) homozygote, and 3 (9.37%) compounds of Hb Adana, Hb CS, and Hb Pakse with co-inheritance Hb E, respectively. Most of the patients with AATA(--AA) compounds with the α-variant exhibited a significant phenotype between moderate to severe thalassaemia, especially cases with compound α<sup>−AA</sup>α/α<sup>Adana</sup>α. <b>Conclusions</b>: AATA(--AA) is a significant pathogenic variant that should be diagnosed to prevent significant thalassaemia phenotype or transfusion-dependent thalassaemia.https://www.mdpi.com/2075-4418/15/10/1284non-deletional α-thalassaemiapolyadenylation mutationAATA(--AA)Hb H disease |
| spellingShingle | Norafiza Mohd Yasin Syahzuwan Hassan Nur Aisyah Aziz Faidatul Syazlin Abdul Hamid Ezalia Esa Ezzanie Suffya Zulkefli Rohana Ghazali Syirah Nazirah Tajuddin Mohd Nazif Darawi Yuslina Mat Yusoff Cornelis L. Harteveld The Clinical and Laboratory Profiles of a Deletional α2-Globin Gene Polyadenylation Signal Sequence (AATAAA > AATA--) [HBA2:c.*93_*94delAA]: The Malaysian Experience Diagnostics non-deletional α-thalassaemia polyadenylation mutation AATA(--AA) Hb H disease |
| title | The Clinical and Laboratory Profiles of a Deletional α2-Globin Gene Polyadenylation Signal Sequence (AATAAA > AATA--) [HBA2:c.*93_*94delAA]: The Malaysian Experience |
| title_full | The Clinical and Laboratory Profiles of a Deletional α2-Globin Gene Polyadenylation Signal Sequence (AATAAA > AATA--) [HBA2:c.*93_*94delAA]: The Malaysian Experience |
| title_fullStr | The Clinical and Laboratory Profiles of a Deletional α2-Globin Gene Polyadenylation Signal Sequence (AATAAA > AATA--) [HBA2:c.*93_*94delAA]: The Malaysian Experience |
| title_full_unstemmed | The Clinical and Laboratory Profiles of a Deletional α2-Globin Gene Polyadenylation Signal Sequence (AATAAA > AATA--) [HBA2:c.*93_*94delAA]: The Malaysian Experience |
| title_short | The Clinical and Laboratory Profiles of a Deletional α2-Globin Gene Polyadenylation Signal Sequence (AATAAA > AATA--) [HBA2:c.*93_*94delAA]: The Malaysian Experience |
| title_sort | clinical and laboratory profiles of a deletional α2 globin gene polyadenylation signal sequence aataaa aata hba2 c 93 94delaa the malaysian experience |
| topic | non-deletional α-thalassaemia polyadenylation mutation AATA(--AA) Hb H disease |
| url | https://www.mdpi.com/2075-4418/15/10/1284 |
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