Background Thalassaemia and variant haemoglobin are the most common severe monogenic disorders worldwide.
Aims To develop prenatal diagnosis programmes for the prevention of the most important haemoglobin disorders and identify healthy carriers of thalassaemia.
Methods Sequencing analysis was used to obtain complete data on gene structure and to correlate specific phenotypic expression with mutations, especially for new or very rare mutations in globin genes.
Results A rare single nucleotide variation, HBB:c.93–23T>C, located in nucleotide 108 of the first intervening sequence of the HBB gene, was identified. This variation was previously reported but its clinical significance was not known. Six heterozygous patients had this nucleotide variation and eight further cases co-inherited it together with other defects in the globin genes. Heterozygous subjects for this substitution showed normal haematological and electrophoretic features, whereas subjects who were compound heterozygotes for this mutation and another defect in globin genes showed the classic phenotype of a healthy carrier.
Conclusion This nucleotide can be considered a single nucleotide polymorphism and not a thalassaemic mutation that reduces the production of haemoglobin. This is another example of a very rare nucleotide variation. Knowledge of this is important so that appropriate genetic counselling can be carried out of a couple potentially at risk, where one of the partners is a carrier of β-thalassaemia and the other is carrier of a nucleotide variation.
- thalassaemia, single nucleotide variation
- prenatal diagnosis
- prenatal genetic counseling
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Handling editor Mary Frances McMullin.
Contributors FC, MC and FL performed the experiments; MV and AG wrote the paper; AG, DR and GC designed the study and provided the clinical background; CP and AM revised the manuscript.
Competing interests None declared.
Ethics approval Institutional review board (Hospital Ethical Committee).
Provenance and peer review Not commissioned; externally peer reviewed.