Alpha thalassaemia due to non-deletional mutations on the -3.7 alpha globin fusion gene: laboratory diagnosis and clinical importance

Aims:Alpha () thalassaemia may be caused by large deletions of the globin gene(s), or rarely, non-deletional mutations. Both types of mutations may co-exist, and if located on the same allele ((0)), produce a reproductive risk of hydrops fetalis. We illustrate how clinical-laboratory correlation and accurate gene sequencing are essential in identifying such patients.Method:Nine asymptomatic patients with -(3.7) thalassaemia trait were noted to have significant microcytosis that was insufficiently explained by a single deletion. Hence 1 and 2 globin gene sequencing were performed, which detected a non-deletional mutation in all patients. A new set of 1 specific primers were designed for separate sequencing of the 1 gene and the -(3.7) fusion gene, respectively, so that the non-deletional mutation could be localised to the correct allele.Results:In six of nine patients tested, the non-deletional mutation was on the 1 globin gene. In three patients the mutation was located on the -(3.7) fusion gene. The latter group functionally has an (0) allele (/-) with a reproductive risk for Hb Barts hydrops fetalis.Conclusion:Non-deletional mutations can occur on the globin gene or a fusion gene such as the -(3.7) allele. Identification and accurate localisation of these mutations is important as this can have significant reproductive implications.