Molecular basis of non-deletional HPFH in Thailand and identification of two novel mutations at the binding sites of CCAAT and GATA-1 transcription factors
Abstract High Hb F determinants are genetic defects associated with increased expression of hemoglobin F in adult life, classified as deletional and non-deletional forms. We report the first description of non-deletional hereditary persistence of fetal hemoglobin (HFPH) in Thailand. Study was done o...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-39173-8 |
| _version_ | 1797769558977675264 |
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| author | Kritsada Singha Anupong Pansuwan Mattanee Chewasateanchai Goonnapa Fucharoen Supan Fucharoen |
| author_facet | Kritsada Singha Anupong Pansuwan Mattanee Chewasateanchai Goonnapa Fucharoen Supan Fucharoen |
| author_sort | Kritsada Singha |
| collection | DOAJ |
| description | Abstract High Hb F determinants are genetic defects associated with increased expression of hemoglobin F in adult life, classified as deletional and non-deletional forms. We report the first description of non-deletional hereditary persistence of fetal hemoglobin (HFPH) in Thailand. Study was done on 388 subjects suspected of non-deletional HPFH with elevated Hb F expression. Mutations in the Gγ- and Aγ-globin genes were examined by DNA analysis and rapid diagnosis of HPFH mutations were developed by PCR-based methods. Twenty subjects with five different mutations were identified including three known mutations, − 202 Aγ (C>T) (n = 3), − 196 Aγ (C>T) (n = 3), and − 158 Aγ (C>T) (n = 12), and two novel mutations, − 117 Aγ (G>C) (n = 1) and − 530 Gγ (A>G) (n = 1). Interaction of the − 117 Aγ (G>C) and Hb E (HBB:c.79G>A) resulted in elevation of Hb F to the level of 13.5%. Two plain heterozygous subjects with − 530 Gγ (A>G) had marginally elevated Hb F with 1.9% and 3.0%, whereas the proband with homozygous − 530 Gγ (A>G) had elevated Hb F of 11.5%. Functional prediction indicated that the − 117 Aγ (G>C) and − 530 Gγ (A>G) mutations dramatically alter the binding of transcription factors to respective γ-globin gene promotors, especially the CCAAT and GATA-1 transcription factors. Diverse heterogeneity of non-deletional HFPH with both known and new mutations, and complex interactions of them with other forms of thalassemia are encountered in Thai population. |
| first_indexed | 2024-03-12T21:10:48Z |
| format | Article |
| id | doaj.art-388557aaf6c94b57acef760bf4658ae0 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-12T21:10:48Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-388557aaf6c94b57acef760bf4658ae02023-07-30T11:12:25ZengNature PortfolioScientific Reports2045-23222023-07-0113111010.1038/s41598-023-39173-8Molecular basis of non-deletional HPFH in Thailand and identification of two novel mutations at the binding sites of CCAAT and GATA-1 transcription factorsKritsada Singha0Anupong Pansuwan1Mattanee Chewasateanchai2Goonnapa Fucharoen3Supan Fucharoen4Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen UniversityCentre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen UniversityRegional Health Promotion Center 7, Ministry of Public HealthCentre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen UniversityCentre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen UniversityAbstract High Hb F determinants are genetic defects associated with increased expression of hemoglobin F in adult life, classified as deletional and non-deletional forms. We report the first description of non-deletional hereditary persistence of fetal hemoglobin (HFPH) in Thailand. Study was done on 388 subjects suspected of non-deletional HPFH with elevated Hb F expression. Mutations in the Gγ- and Aγ-globin genes were examined by DNA analysis and rapid diagnosis of HPFH mutations were developed by PCR-based methods. Twenty subjects with five different mutations were identified including three known mutations, − 202 Aγ (C>T) (n = 3), − 196 Aγ (C>T) (n = 3), and − 158 Aγ (C>T) (n = 12), and two novel mutations, − 117 Aγ (G>C) (n = 1) and − 530 Gγ (A>G) (n = 1). Interaction of the − 117 Aγ (G>C) and Hb E (HBB:c.79G>A) resulted in elevation of Hb F to the level of 13.5%. Two plain heterozygous subjects with − 530 Gγ (A>G) had marginally elevated Hb F with 1.9% and 3.0%, whereas the proband with homozygous − 530 Gγ (A>G) had elevated Hb F of 11.5%. Functional prediction indicated that the − 117 Aγ (G>C) and − 530 Gγ (A>G) mutations dramatically alter the binding of transcription factors to respective γ-globin gene promotors, especially the CCAAT and GATA-1 transcription factors. Diverse heterogeneity of non-deletional HFPH with both known and new mutations, and complex interactions of them with other forms of thalassemia are encountered in Thai population.https://doi.org/10.1038/s41598-023-39173-8 |
| spellingShingle | Kritsada Singha Anupong Pansuwan Mattanee Chewasateanchai Goonnapa Fucharoen Supan Fucharoen Molecular basis of non-deletional HPFH in Thailand and identification of two novel mutations at the binding sites of CCAAT and GATA-1 transcription factors Scientific Reports |
| title | Molecular basis of non-deletional HPFH in Thailand and identification of two novel mutations at the binding sites of CCAAT and GATA-1 transcription factors |
| title_full | Molecular basis of non-deletional HPFH in Thailand and identification of two novel mutations at the binding sites of CCAAT and GATA-1 transcription factors |
| title_fullStr | Molecular basis of non-deletional HPFH in Thailand and identification of two novel mutations at the binding sites of CCAAT and GATA-1 transcription factors |
| title_full_unstemmed | Molecular basis of non-deletional HPFH in Thailand and identification of two novel mutations at the binding sites of CCAAT and GATA-1 transcription factors |
| title_short | Molecular basis of non-deletional HPFH in Thailand and identification of two novel mutations at the binding sites of CCAAT and GATA-1 transcription factors |
| title_sort | molecular basis of non deletional hpfh in thailand and identification of two novel mutations at the binding sites of ccaat and gata 1 transcription factors |
| url | https://doi.org/10.1038/s41598-023-39173-8 |
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