Background β+-Thalassaemia is characterised by reduced production of β chains, which decrease can be caused by mutations in the promoter region (CACCC or TATA box), and is classified as mild or silent depending on the extent of β-globin chain reduction. In both cases, homozygotes or compound heterozygotes for these mutations usually have thalassaemia intermedia. Frequently the diagnosis is made in adulthood or even in old age. A total of 37 alterations in the promoter region have been described so far.
Aims In this report we describe the mutations found in the promoter region of the β-globin gene in a single hospital in Madrid.
Methods Between 1998 and 2015, more than 9000 blood samples were analysed for full blood count and underwent haemoglobin electrophoresis and high performance liquid chromatography. Genetic analysis of the β and Gγ-globin genes was carried out by automatic sequencing and, in the case of α genes, by multiplex PCR.
Results 35 samples showed mutation in the promoter region of the β-globin gene, with a total of six different mutations identified: one in the distal CACCC box, two in the proximal CACCC box, three in the ATA box.
Conclusions Any alterations in the proximal CACCC and TATA boxes lead to a moderate decrease in synthesis of the β-globin chain, which has been demonstrated in cases of thalassaemia intermedia that have presented in the second decade of life with a moderate clinical course.
- SICKLE CELL DISEASE
- MOLECULAR GENETICS
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Handling editor Mary Frances McMullin.
Contributors All authors contributed to this work.
Funding This work has been funded by a grant from Instituto de Salud Carlos III (PI12 / 01068) of the Ministry of Economy and Competitiveness.
Competing interests None declared.
Patient consent Obtained.
Ethics approval The Ethics Committee of Hospital Clínico San Carlos, Madrid approved this study.
Provenance and peer review Not commissioned; externally peer reviewed.
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