The Hematological and Molecular Spectrum of α-Thalassemias in Turkey: The Hacettepe Experience
INTRODUCTION: The spectrum of α-thalassemias correlates well with the number of affected α-globin genes. Additionally, combinations of the several non-deletional types of mutations with a large trans deletion comprising the 2 α-globin genes have an impact on the clinical s...
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| Format: | Article |
| Language: | English |
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Galenos Publishing House
2015-05-01
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| Series: | Turkish Journal of Hematology |
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| Online Access: | https://jag.journalagent.com/z4/download_fulltext.asp?pdir=tjh&un=TJH-56688 |
| _version_ | 1828025512331575296 |
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| author | Şule Ünal Fatma Gümrük |
| author_facet | Şule Ünal Fatma Gümrük |
| author_sort | Şule Ünal |
| collection | DOAJ |
| description | INTRODUCTION: The spectrum of α-thalassemias correlates well with the number of affected α-globin genes. Additionally, combinations of the several non-deletional types of mutations with a large trans deletion comprising the 2 α-globin genes have an impact on the clinical severity. The objective of this study was to analyze the hematological and molecular data of 35 patients with Hb H disease from a single center in order to identify the genotypes of Hb H disease and genotype-phenotype correlations. METHODS: Herein, we report the hematological and mutational spectrum of patients with Hb H disease (n=35). Additionally, genotypes of α-gene mutations of 78 individuals, who were referred to our institution for α-gene screening, were analyzed. RESULTS: Supporting the previous data from Turkey, -α3.7 was the most common mutation among patients with Hb H disease (62.8%) and in the other 78 subjects (39.7%). Of the patients with Hb H disease, the most common genotypes were -α3.7/--20.5, -α3.7/--26.5, and -α3.7/--17.5 in 10 (28.6%), 6 (17.1%), and 6 (17.1%) patients, respectively. Another small deletion, -4.2 alpha, and several non-deletional types of α-gene mutations, namely α (-5nt): IVS-I donor site (GAG.GTG.AGG->GAG.G-----); α (PA-2): AATAAA>AATGGA, and α (cd59): GGC->GAC, were found to be associated with Hb H disease when present at trans loci of one of the large deletions given above. The combinations consisting of 1 non-deletional and 1 of the large deletional types of mutations (αTα/--) at trans loci were found to result in a more severe phenotype compared to the genotypes composed of 1 small trans deletion of a large deletion (-α/--). The combination of α (Cd59) and -- in trans was associated with severe phenotype and the disease was associated with an increase in Hb Bart's level with null Hb H. In spite of the presence of 2 intact α-globin genes, homozygosity for PA-2 mutation resulted in severe Hb H disease. DISCUSSION AND CONCLUSION: This study indicated that Hb H disease is not rare in Turkey and its genotype is quite heterogeneous. |
| first_indexed | 2024-04-10T13:02:38Z |
| format | Article |
| id | doaj.art-62de417c85a84f56b875f749f5aae59e |
| institution | Directory Open Access Journal |
| issn | 1308-5263 |
| language | English |
| last_indexed | 2024-04-10T13:02:38Z |
| publishDate | 2015-05-01 |
| publisher | Galenos Publishing House |
| record_format | Article |
| series | Turkish Journal of Hematology |
| spelling | doaj.art-62de417c85a84f56b875f749f5aae59e2023-02-15T16:13:06ZengGalenos Publishing HouseTurkish Journal of Hematology1308-52632015-05-0132213614310.4274/tjh.2014.0200TJH-56688The Hematological and Molecular Spectrum of α-Thalassemias in Turkey: The Hacettepe ExperienceŞule Ünal0Fatma Gümrük1Hacettepe University Faculty of Medicine, Division of Pediatric Hematology, Ankara, TurkeyHacettepe University Faculty of Medicine, Division of Pediatric Hematology, Ankara, TurkeyINTRODUCTION: The spectrum of α-thalassemias correlates well with the number of affected α-globin genes. Additionally, combinations of the several non-deletional types of mutations with a large trans deletion comprising the 2 α-globin genes have an impact on the clinical severity. The objective of this study was to analyze the hematological and molecular data of 35 patients with Hb H disease from a single center in order to identify the genotypes of Hb H disease and genotype-phenotype correlations. METHODS: Herein, we report the hematological and mutational spectrum of patients with Hb H disease (n=35). Additionally, genotypes of α-gene mutations of 78 individuals, who were referred to our institution for α-gene screening, were analyzed. RESULTS: Supporting the previous data from Turkey, -α3.7 was the most common mutation among patients with Hb H disease (62.8%) and in the other 78 subjects (39.7%). Of the patients with Hb H disease, the most common genotypes were -α3.7/--20.5, -α3.7/--26.5, and -α3.7/--17.5 in 10 (28.6%), 6 (17.1%), and 6 (17.1%) patients, respectively. Another small deletion, -4.2 alpha, and several non-deletional types of α-gene mutations, namely α (-5nt): IVS-I donor site (GAG.GTG.AGG->GAG.G-----); α (PA-2): AATAAA>AATGGA, and α (cd59): GGC->GAC, were found to be associated with Hb H disease when present at trans loci of one of the large deletions given above. The combinations consisting of 1 non-deletional and 1 of the large deletional types of mutations (αTα/--) at trans loci were found to result in a more severe phenotype compared to the genotypes composed of 1 small trans deletion of a large deletion (-α/--). The combination of α (Cd59) and -- in trans was associated with severe phenotype and the disease was associated with an increase in Hb Bart's level with null Hb H. In spite of the presence of 2 intact α-globin genes, homozygosity for PA-2 mutation resulted in severe Hb H disease. DISCUSSION AND CONCLUSION: This study indicated that Hb H disease is not rare in Turkey and its genotype is quite heterogeneous.https://jag.journalagent.com/z4/download_fulltext.asp?pdir=tjh&un=TJH-56688molecularmutationα-thalassemiaturkey |
| spellingShingle | Şule Ünal Fatma Gümrük The Hematological and Molecular Spectrum of α-Thalassemias in Turkey: The Hacettepe Experience Turkish Journal of Hematology molecular mutation α -thalassemia turkey |
| title | The Hematological and Molecular Spectrum of α-Thalassemias in Turkey: The Hacettepe Experience |
| title_full | The Hematological and Molecular Spectrum of α-Thalassemias in Turkey: The Hacettepe Experience |
| title_fullStr | The Hematological and Molecular Spectrum of α-Thalassemias in Turkey: The Hacettepe Experience |
| title_full_unstemmed | The Hematological and Molecular Spectrum of α-Thalassemias in Turkey: The Hacettepe Experience |
| title_short | The Hematological and Molecular Spectrum of α-Thalassemias in Turkey: The Hacettepe Experience |
| title_sort | hematological and molecular spectrum of 945 thalassemias in turkey the hacettepe experience |
| topic | molecular mutation α -thalassemia turkey |
| url | https://jag.journalagent.com/z4/download_fulltext.asp?pdir=tjh&un=TJH-56688 |
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