Molecular Characterization of Hb Hamilton Hill (HBA2: c.388delC), a NovelHBA2Variant Generating a Premature Termination Codon and TruncatedHBA2Chain

Hemoglobin ◽  
2015 ◽  
Vol 39 (2) ◽  
pp. 88-94 ◽  
Author(s):  
Talal Qadah ◽  
Jill Finlayson ◽  
Emma North ◽  
Reza Ghassemifar
RNA Biology ◽  
2017 ◽  
Vol 14 (3) ◽  
pp. 378-388 ◽  
Author(s):  
Laure Bidou ◽  
Olivier Bugaud ◽  
Valery Belakhov ◽  
Timor Baasov ◽  
Olivier Namy

Blood ◽  
2009 ◽  
Vol 114 (19) ◽  
pp. 4179-4185 ◽  
Author(s):  
Sanjai Sharma ◽  
Alan Lichtenstein

Abstract Premature termination codon (PTC) mutations are due to insertion or deletion of nucleotides causing a frameshift and premature termination codon in RNA. These transcripts are degraded by the nonsense-mediated decay pathway and have a very short half-life. We used a microarray technique to screen for genes that up-regulate their RNA signal upon nonsense-mediated decay pathway blockade in chronic lymphocytic leukemia (CLL) specimens and identified an E-cadherin transcript with PTC. Sequencing revealed an aberrant E-cadherin transcript lacking exon 11, resulting in a frameshift and PTC. The aberrant E-cadherin transcript was also identified in normal B cells, but occurred at a much lower level compared with CLL cells. In CLL specimens, E-cadherin expression was depressed more than 50% in 62% cases (relative to normal B cells). By real-time polymerase chain reaction analysis, the relative amounts of wild-type transcript inversely correlated with amounts of aberrant transcript (P = .018). Ectopic expression of E-cadherin in CLL specimens containing high amounts of aberrant transcript resulted in down-regulation of the wnt–β-catenin pathway reporter, a pathway known to be up-regulated in CLL. Our data point to a novel mechanism of E-cadherin gene inactivation, with CLL cells displaying a higher proportion of aberrant nonfunctional transcripts and resulting up-regulation of the wnt–β-catenin pathway.


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