Gamma delta beta-thalassemia due to a de novo mutation deleting the 5' beta-globin gene activation-region hypersensitive sites.
Open accessAbstract
gamma delta beta-Thalassemia is a rare disorder of hemoglobin biosynthesis, characterized molecularly by partial or complete deletions of the beta-globin gene complex of 100 kilobases (kb) or greater. Common to all mutants described has been the deletion of the most-5' sequences of the beta-globin complex. We have used the techniques of pulsed-field gel electrophoresis and polymerase chain reaction to study a patient with a clinical gamma delta beta-thalassemia phenotype. This subject developed a de novo deletion on a maternally inherited beta-globin gene chromosome involving approximately 30 kb of sequences 5' to the epsilon gene; the deletion extends from -9.5 kb to -39 kb 5' of epsilon and includes three of the four DNase I hypersensitive sites (at -10.9 kb, -14.7 kb, and -18 kb 5' of epsilon). The remaining sequences of the beta-globin complex, including the DNase I hypersensitive sites at -6.1 kb and all structural genes in cis to the deletion are physically intact, but presumably nonfunctional, as evidenced by the presence of a beta S-globin gene that is not expressed as a sickle hemoglobin. Deletion of DNase I hypersensitive sites on a previously functional beta-globin gene complex confirms the significance of these sites in regulating globin gene expression.
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Non-coding enhancer deletions have been linked to severe human disease phenotypes such as beta thalassaemia and polydactyly.
“It soon became clear that enhancers also played vital roles in humans, with non-coding enhancer deletions starting to be linked to severe disease phenotypes such as beta thalassaemia and polydactyly [25–28].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [26]
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β-Globin gene inactivation by DNA translocation in γβ-thalassaemi
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Towards a comprehensive catalogue of validated and target-linked human enhancers
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Transcriptional enhancers and their communication with gene promoters
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- Authors
- Driscoll, M. C., Dobkin, C. S., & Alter, B. P.
- Affiliations
- Albert Einstein College of Medicine (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1989-10
- Volume
- 86
- Issue
- 19
- Pages
- 7470-7474
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC298086
- OpenAlex
- W2141609688
- Cited by
- 233
- References
- 1
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 2 · 2022: 7 · 2021: 6 · 2020: 4 · 2019: 5 · 2018: 1 · 2017: 5 · 2016: 7 · 2015: 5 · 2014: 2 · 2013: 5 · 2012: 6
- FWCI
- 14.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL 38655., HL 26132, HL38265)
- Topics
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- de novo deletion, DNase I hypersensitive sites, globin gene regulation, epsilon-globin gene, beta-globin gene expression
- MeSH terms
- Base Sequence, Chromosome Deletion, Gene Expression Regulation, Genes, Globins, Haplotypes, Humans, Molecular Sequence Data, Mutation, Phenotype, Thalassemia, Restriction Mapping, Oligonucleotide Probes, Transcriptional Activation, Polymerase Chain Reaction
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