Molecular and cellular characterization of a new a-Thalassemia mutation (HBA2:c.94A>C) generating an alternative splice site and a premature stop codon
The identification of a-thalassemia (a-thal) due to point mutations has been increasing significantly with the advancement of molecular diagnostic tools. We describe here the molecular and cellular characteristics of the thalassemia mutation HBA2:c.94A>C, a novel point mutation affecting the...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal Article |
| Published: |
2012
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| Online Access: | http://hdl.handle.net/20.500.11937/16218 |
| _version_ | 1848749112853266432 |
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| author | Qadah, T. Finlayson, J. Newbound, C. Pell, N. Pascoe, M. Greenwood, L. Holmes, P. Grey, D. Beilby, J. Ghassemifar, Reza |
| author_facet | Qadah, T. Finlayson, J. Newbound, C. Pell, N. Pascoe, M. Greenwood, L. Holmes, P. Grey, D. Beilby, J. Ghassemifar, Reza |
| author_sort | Qadah, T. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | The identification of a-thalassemia (a-thal) due to point mutations has been increasing significantly with the advancement of molecular diagnostic tools. We describe here the molecular and cellular characteristics of the thalassemia mutation HBA2:c.94A>C, a novel point mutation affecting the a2-globin gene, causing a mild a-thal phenotype in a male patient of undisclosed ethnicity, investigated for unexplained microcytosis. The detected mutation is located at the penultimate nucleotide (nt) of the first exon which we postulated might affect pre mRNA splicing. While an in silico analysis did not predict any aberrant splice variants, experimental analysis using our in vitro model for gene expression studies showed utilization of a cryptic splice site at codon 15 that resulted in an aberrant splice variant. As a result, a frameshift in the reading frame of the mature mRNA was produced, leading to the formation of a premature termination codon (PTC) between codons 48 and 49 in exon 2. This in turn leads to nonsense mediated mRNA decay (NMD) and the phenotype of a-thal. Copyright © Informa Healthcare USA, Inc. |
| first_indexed | 2025-11-14T07:15:46Z |
| format | Journal Article |
| id | curtin-20.500.11937-16218 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T07:15:46Z |
| publishDate | 2012 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-162182017-09-13T15:04:06Z Molecular and cellular characterization of a new a-Thalassemia mutation (HBA2:c.94A>C) generating an alternative splice site and a premature stop codon Qadah, T. Finlayson, J. Newbound, C. Pell, N. Pascoe, M. Greenwood, L. Holmes, P. Grey, D. Beilby, J. Ghassemifar, Reza The identification of a-thalassemia (a-thal) due to point mutations has been increasing significantly with the advancement of molecular diagnostic tools. We describe here the molecular and cellular characteristics of the thalassemia mutation HBA2:c.94A>C, a novel point mutation affecting the a2-globin gene, causing a mild a-thal phenotype in a male patient of undisclosed ethnicity, investigated for unexplained microcytosis. The detected mutation is located at the penultimate nucleotide (nt) of the first exon which we postulated might affect pre mRNA splicing. While an in silico analysis did not predict any aberrant splice variants, experimental analysis using our in vitro model for gene expression studies showed utilization of a cryptic splice site at codon 15 that resulted in an aberrant splice variant. As a result, a frameshift in the reading frame of the mature mRNA was produced, leading to the formation of a premature termination codon (PTC) between codons 48 and 49 in exon 2. This in turn leads to nonsense mediated mRNA decay (NMD) and the phenotype of a-thal. Copyright © Informa Healthcare USA, Inc. 2012 Journal Article http://hdl.handle.net/20.500.11937/16218 10.3109/03630269.2012.670683 restricted |
| spellingShingle | Qadah, T. Finlayson, J. Newbound, C. Pell, N. Pascoe, M. Greenwood, L. Holmes, P. Grey, D. Beilby, J. Ghassemifar, Reza Molecular and cellular characterization of a new a-Thalassemia mutation (HBA2:c.94A>C) generating an alternative splice site and a premature stop codon |
| title | Molecular and cellular characterization of a new a-Thalassemia mutation (HBA2:c.94A>C) generating an alternative splice site and a premature stop codon |
| title_full | Molecular and cellular characterization of a new a-Thalassemia mutation (HBA2:c.94A>C) generating an alternative splice site and a premature stop codon |
| title_fullStr | Molecular and cellular characterization of a new a-Thalassemia mutation (HBA2:c.94A>C) generating an alternative splice site and a premature stop codon |
| title_full_unstemmed | Molecular and cellular characterization of a new a-Thalassemia mutation (HBA2:c.94A>C) generating an alternative splice site and a premature stop codon |
| title_short | Molecular and cellular characterization of a new a-Thalassemia mutation (HBA2:c.94A>C) generating an alternative splice site and a premature stop codon |
| title_sort | molecular and cellular characterization of a new a-thalassemia mutation (hba2:c.94a>c) generating an alternative splice site and a premature stop codon |
| url | http://hdl.handle.net/20.500.11937/16218 |