Abstract:
: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 49 bp 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 α-thalassemia (α-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.
journal_name
Hemoglobinjournal_title
Hemoglobinauthors
Qadah T,Finlayson J,Joly P,Ghassemifar Rdoi
10.3109/03630269.2013.858639subject
Has Abstractpub_date
2014-01-01 00:00:00pages
13-8issue
1eissn
0363-0269issn
1532-432Xjournal_volume
38pub_type
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