Case report: Identification of a novel triplication of alpha-globin gene by the third-generation sequencing: pedigree analysis and genetic diagnosis
ABSTRACTBackground Thalassemia, a common autosomal hereditary blood disorder worldwide, mainly contains α- and β-thalassemia. The α-globin gene triplicates allele is harmless for carriers, but aggravates the phenotype of β-thalassemia. Therefore, it is particularly crucial to accurately detect the s...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Hematology |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/16078454.2023.2277571 |
| _version_ | 1797401423989702656 |
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| author | Yujiao Chen Tiantian Xie Minhui Ma Juan Yang Yihang Lv Xudong Dong |
| author_facet | Yujiao Chen Tiantian Xie Minhui Ma Juan Yang Yihang Lv Xudong Dong |
| author_sort | Yujiao Chen |
| collection | DOAJ |
| description | ABSTRACTBackground Thalassemia, a common autosomal hereditary blood disorder worldwide, mainly contains α- and β-thalassemia. The α-globin gene triplicates allele is harmless for carriers, but aggravates the phenotype of β-thalassemia. Therefore, it is particularly crucial to accurately detect the structural variants of α-globin gene clusters.Case report We reported a 28-year-old man, the proband, with microcytic hypochromic anemia. From pedigree analysis, his mother and sister had hypochromic microcytosis, and his father was normal. Genetic testing of thalassemia identified a novel α-globin gene triplicate named αααanti4.2del726bp (NC_000016.10:g.170769_174300dupinsAAAAAA) by third-generation sequencing (TGS) in the proband and his father, which was further validated by multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing. The genotypes of the proband’s mother and sister were both -α3.7/αα compounded with heterozygous HBB:c.126_129delCTTT. They were categorized as silent α-thalassemia with co-inheritance of β-thalassemia trait. The proband’s genotype additionally had the α-globin gene triplicates compared with his mother and sister, which increased the imbalance between α/β-globin, so the proband had more severe hematological parameters. The proband’s wife was diagnosed as HBA2:c.427T > C heterozygosis, and his daughter had the novel α-globin gene triplicates compounded with HBA2:c.427T > C, therefore the girl might be asymptomatic.Conclusion The identification of the novel α-globin gene triplicates provides more insight for the research of thalassemia variants and indicates that TGS has significant advantages on genetic testing of thalassemia for the reliability, accuracy and comprehensiveness. |
| first_indexed | 2024-03-09T02:09:53Z |
| format | Article |
| id | doaj.art-7f0792f5951749efaabee65dd3d47f9a |
| institution | Directory Open Access Journal |
| issn | 1607-8454 |
| language | English |
| last_indexed | 2024-03-09T02:09:53Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Hematology |
| spelling | doaj.art-7f0792f5951749efaabee65dd3d47f9a2023-12-07T14:00:14ZengTaylor & Francis GroupHematology1607-84542023-12-0128110.1080/16078454.2023.2277571Case report: Identification of a novel triplication of alpha-globin gene by the third-generation sequencing: pedigree analysis and genetic diagnosisYujiao Chen0Tiantian Xie1Minhui Ma2Juan Yang3Yihang Lv4Xudong Dong5Dehong Medical Group Hospital of Traditional Chinese Medicine, Dehong Dai and Jingpo Autonomous Prefecture, People’s Republic of ChinaBerry Genomics Corporation, Beijing, People’s Republic of ChinaBerry Genomics Corporation, Beijing, People’s Republic of ChinaKunming Kingmed Institute for Clinical Laboratory, Kunming, People’s Republic of ChinaDepartment of Obstetrical, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, People’s Republic of ChinaDepartment of Obstetrical, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, People’s Republic of ChinaABSTRACTBackground Thalassemia, a common autosomal hereditary blood disorder worldwide, mainly contains α- and β-thalassemia. The α-globin gene triplicates allele is harmless for carriers, but aggravates the phenotype of β-thalassemia. Therefore, it is particularly crucial to accurately detect the structural variants of α-globin gene clusters.Case report We reported a 28-year-old man, the proband, with microcytic hypochromic anemia. From pedigree analysis, his mother and sister had hypochromic microcytosis, and his father was normal. Genetic testing of thalassemia identified a novel α-globin gene triplicate named αααanti4.2del726bp (NC_000016.10:g.170769_174300dupinsAAAAAA) by third-generation sequencing (TGS) in the proband and his father, which was further validated by multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing. The genotypes of the proband’s mother and sister were both -α3.7/αα compounded with heterozygous HBB:c.126_129delCTTT. They were categorized as silent α-thalassemia with co-inheritance of β-thalassemia trait. The proband’s genotype additionally had the α-globin gene triplicates compared with his mother and sister, which increased the imbalance between α/β-globin, so the proband had more severe hematological parameters. The proband’s wife was diagnosed as HBA2:c.427T > C heterozygosis, and his daughter had the novel α-globin gene triplicates compounded with HBA2:c.427T > C, therefore the girl might be asymptomatic.Conclusion The identification of the novel α-globin gene triplicates provides more insight for the research of thalassemia variants and indicates that TGS has significant advantages on genetic testing of thalassemia for the reliability, accuracy and comprehensiveness.https://www.tandfonline.com/doi/10.1080/16078454.2023.2277571Thalassemiaα-globin gene triplicatesβ-thalassemiabreakpointthird-generation sequencing |
| spellingShingle | Yujiao Chen Tiantian Xie Minhui Ma Juan Yang Yihang Lv Xudong Dong Case report: Identification of a novel triplication of alpha-globin gene by the third-generation sequencing: pedigree analysis and genetic diagnosis Hematology Thalassemia α-globin gene triplicates β-thalassemia breakpoint third-generation sequencing |
| title | Case report: Identification of a novel triplication of alpha-globin gene by the third-generation sequencing: pedigree analysis and genetic diagnosis |
| title_full | Case report: Identification of a novel triplication of alpha-globin gene by the third-generation sequencing: pedigree analysis and genetic diagnosis |
| title_fullStr | Case report: Identification of a novel triplication of alpha-globin gene by the third-generation sequencing: pedigree analysis and genetic diagnosis |
| title_full_unstemmed | Case report: Identification of a novel triplication of alpha-globin gene by the third-generation sequencing: pedigree analysis and genetic diagnosis |
| title_short | Case report: Identification of a novel triplication of alpha-globin gene by the third-generation sequencing: pedigree analysis and genetic diagnosis |
| title_sort | case report identification of a novel triplication of alpha globin gene by the third generation sequencing pedigree analysis and genetic diagnosis |
| topic | Thalassemia α-globin gene triplicates β-thalassemia breakpoint third-generation sequencing |
| url | https://www.tandfonline.com/doi/10.1080/16078454.2023.2277571 |
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