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

Aims: 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 (α0), produce a reproductive risk of hydrops fetalis. We illustrate how clinical-laboratory correlation...

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Main Authors: Chow, A., Ghassemifar, Reza, Finlayson, J.
Format: Journal Article
Published: 2013
Online Access:http://hdl.handle.net/20.500.11937/38804
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author Chow, A.
Ghassemifar, Reza
Finlayson, J.
author_facet Chow, A.
Ghassemifar, Reza
Finlayson, J.
author_sort Chow, A.
building Curtin Institutional Repository
collection Online Access
description Aims: 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 (α0), produce a reproductive risk of hydrops fetalis. We illustrate how clinical-laboratory correlation and accurate α gene sequencing are essential in identifying such patients. Method: Nine asymptomatic patients with - α 3.7 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 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 α1 globin gene. In three patients the mutation was located on the - α 3.7 fusion gene. The latter group functionally has an α0 allele (αα/–) with a reproductive risk for Hb Barts hydrops fetalis. Conclusion: Non-deletional mutations can occur on the α globin gene or a fusion gene such as the - α3.7 allele. Identification and accurate localisation of these mutations is important as this can have significant reproductive implications.
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spelling curtin-20.500.11937-388042017-09-13T14:15:45Z Alpha thalassaemia due to non-deletional mutations on the -3.7 alpha globin fusion gene: Laboratory diagnosis and clinical importance Chow, A. Ghassemifar, Reza Finlayson, J. Aims: 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 (α0), produce a reproductive risk of hydrops fetalis. We illustrate how clinical-laboratory correlation and accurate α gene sequencing are essential in identifying such patients. Method: Nine asymptomatic patients with - α 3.7 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 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 α1 globin gene. In three patients the mutation was located on the - α 3.7 fusion gene. The latter group functionally has an α0 allele (αα/–) with a reproductive risk for Hb Barts hydrops fetalis. Conclusion: Non-deletional mutations can occur on the α globin gene or a fusion gene such as the - α3.7 allele. Identification and accurate localisation of these mutations is important as this can have significant reproductive implications. 2013 Journal Article http://hdl.handle.net/20.500.11937/38804 10.1097/PAT.0b013e32836526d7 restricted
spellingShingle Chow, A.
Ghassemifar, Reza
Finlayson, J.
Alpha thalassaemia due to non-deletional mutations on the -3.7 alpha globin fusion gene: Laboratory diagnosis and clinical importance
title Alpha thalassaemia due to non-deletional mutations on the -3.7 alpha globin fusion gene: Laboratory diagnosis and clinical importance
title_full Alpha thalassaemia due to non-deletional mutations on the -3.7 alpha globin fusion gene: Laboratory diagnosis and clinical importance
title_fullStr Alpha thalassaemia due to non-deletional mutations on the -3.7 alpha globin fusion gene: Laboratory diagnosis and clinical importance
title_full_unstemmed Alpha thalassaemia due to non-deletional mutations on the -3.7 alpha globin fusion gene: Laboratory diagnosis and clinical importance
title_short Alpha thalassaemia due to non-deletional mutations on the -3.7 alpha globin fusion gene: Laboratory diagnosis and clinical importance
title_sort alpha thalassaemia due to non-deletional mutations on the -3.7 alpha globin fusion gene: laboratory diagnosis and clinical importance
url http://hdl.handle.net/20.500.11937/38804