Molecular and cellular analysis of a novel HBA2 mutation (HBA2: C.94A>G) shows activation of a cryptic splice site and generation of a premature termination codon
In this study, we describe the clinical features and provide experimental analyses of a novel point mutation affecting the penultimate nucleotide of the first exon of the HBA2 (HBA2: c.94A>G) gene identified in a 26-year-old female who also carries a heterozygous Hb E (HBB: c.79G>A) va...
| Main Authors: | , , , |
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| Format: | Journal Article |
| Published: |
2014
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| Online Access: | http://hdl.handle.net/20.500.11937/6903 |
| _version_ | 1848745211682881536 |
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| author | Qadah, T. Finlayson, J. Joly, P. Ghassemifar, Reza |
| author_facet | Qadah, T. Finlayson, J. Joly, P. Ghassemifar, Reza |
| author_sort | Qadah, T. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | In this study, we describe the clinical features and provide experimental analyses of a novel point mutation affecting the penultimate nucleotide of the first exon of the HBA2 (HBA2: c.94A>G) gene identified in a 26-year-old female who also carries a heterozygous Hb E (HBB: c.79G>A) variant. The aim of the study was to investigate the impact of this point mutation on the transcriptional activity of the HBA2 gene using a combination of an initial in silico prediction followed by in vitro mutagenesis and transcriptional activity assessment. The analyses revealed that the HBA2: c.94A>G point mutation causes the activation of a cryptic splice site located 49bp upstream of the exon1-intron1 boundary in both HBA2 long and short isoforms, thus generating a frameshift and a premature termination codon between codons 48 and 49 in the second exon. A rapid degradation of the aberrantly spliced transcripts by the nonsense mediated decay (NMD) surveillance system is highly indicative of an a-thalassemia (a-thal) phenotype. However, the abnormal mRNA may not be entirely degraded since the proband presents a slight splenomegaly that could be the sign of extra vascular hemolysis. © 2014 Informa Healthcare USA, Inc. |
| first_indexed | 2025-11-14T06:13:45Z |
| format | Journal Article |
| id | curtin-20.500.11937-6903 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T06:13:45Z |
| publishDate | 2014 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-69032017-09-13T14:42:51Z Molecular and cellular analysis of a novel HBA2 mutation (HBA2: C.94A>G) shows activation of a cryptic splice site and generation of a premature termination codon Qadah, T. Finlayson, J. Joly, P. Ghassemifar, Reza In this study, we describe the clinical features and provide experimental analyses of a novel point mutation affecting the penultimate nucleotide of the first exon of the HBA2 (HBA2: c.94A>G) gene identified in a 26-year-old female who also carries a heterozygous Hb E (HBB: c.79G>A) variant. The aim of the study was to investigate the impact of this point mutation on the transcriptional activity of the HBA2 gene using a combination of an initial in silico prediction followed by in vitro mutagenesis and transcriptional activity assessment. The analyses revealed that the HBA2: c.94A>G point mutation causes the activation of a cryptic splice site located 49bp upstream of the exon1-intron1 boundary in both HBA2 long and short isoforms, thus generating a frameshift and a premature termination codon between codons 48 and 49 in the second exon. A rapid degradation of the aberrantly spliced transcripts by the nonsense mediated decay (NMD) surveillance system is highly indicative of an a-thalassemia (a-thal) phenotype. However, the abnormal mRNA may not be entirely degraded since the proband presents a slight splenomegaly that could be the sign of extra vascular hemolysis. © 2014 Informa Healthcare USA, Inc. 2014 Journal Article http://hdl.handle.net/20.500.11937/6903 10.3109/03630269.2013.858639 restricted |
| spellingShingle | Qadah, T. Finlayson, J. Joly, P. Ghassemifar, Reza Molecular and cellular analysis of a novel HBA2 mutation (HBA2: C.94A>G) shows activation of a cryptic splice site and generation of a premature termination codon |
| title | Molecular and cellular analysis of a novel HBA2 mutation (HBA2: C.94A>G) shows activation of a cryptic splice site and generation of a premature termination codon |
| title_full | Molecular and cellular analysis of a novel HBA2 mutation (HBA2: C.94A>G) shows activation of a cryptic splice site and generation of a premature termination codon |
| title_fullStr | Molecular and cellular analysis of a novel HBA2 mutation (HBA2: C.94A>G) shows activation of a cryptic splice site and generation of a premature termination codon |
| title_full_unstemmed | Molecular and cellular analysis of a novel HBA2 mutation (HBA2: C.94A>G) shows activation of a cryptic splice site and generation of a premature termination codon |
| title_short | Molecular and cellular analysis of a novel HBA2 mutation (HBA2: C.94A>G) shows activation of a cryptic splice site and generation of a premature termination codon |
| title_sort | molecular and cellular analysis of a novel hba2 mutation (hba2: c.94a>g) shows activation of a cryptic splice site and generation of a premature termination codon |
| url | http://hdl.handle.net/20.500.11937/6903 |