title: Alpha thalassaemia due to non-deletional mutations on the -3.7 alpha globin fusion gene: laboratory diagnosis and clinical importance.
abstract: Alpha (α) thalassaemia may be caused by large deletions of the α globin gene(s), or rarely, non-deletional mutations. Both types of mutations may co-exist, and if located on the same allele (α), produce a reproductive risk of hydrops fetalis. We illustrate how clinical-laboratory correlation and accurate α gene sequencing are essential in identifying such patients.
  
  
  
  Nine asymptomatic patients with -α thalassaemia trait were noted to have significant microcytosis that was insufficiently explained by a single α deletion. Hence α1 and α2 globin gene sequencing were performed, which detected a non-deletional mutation in all patients. A new set of α1 specific primers were designed for separate sequencing of the α1 gene and the -α fusion gene, respectively, so that the non-deletional mutation could be localised to the correct allele.
  
  
  
  In six of nine patients tested, the non-deletional mutation was on the α1 globin gene. In three patients the mutation was located on the -α fusion gene. The latter group functionally has an α allele (αα/-) with a reproductive risk for Hb Barts hydrops fetalis.
  
  
  
  Non-deletional mutations can occur on the α globin gene or a fusion gene such as the -α allele. Identification and accurate localisation of these mutations is important as this can have significant reproductive implications.
authors.affiliation: *Department of Haematology, PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, Nedlands †School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands ‡School of Biomedical Sciences, Curtin University, Bentley, Western Australia, Australia.
authors.forename: Annie
authors.initials: A
authors.lastname: Chow
authors.forename: Reza
authors.initials: R
authors.lastname: Ghassemifar
authors.forename: Jill
authors.initials: J
authors.lastname: Finlayson
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult; D055542:alpha-Globins / Q000235:genetics*; D017085:alpha-Thalassemia / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D055542:alpha-Globins