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Two novel C-terminal frameshift mutations in the β-globin gene lead to rapid mRNA decay

Rawa, Katarzyna and Szczęsny, Roman J. and Owczarek, Ewelina P. and Adamowicz-Salach, Anna and Klukowska, Anna and Demkow, Urszula and Plochocka, Danuta and Szczesny, Pawel and Gora, Monika and Dziembowski, Andrzej and Burzynska, Beata (2017) Two novel C-terminal frameshift mutations in the β-globin gene lead to rapid mRNA decay. BMC Medical Genetics, 18 (1). p. 65. ISSN 1471-2350


Official URL: http://doi.org/10.1186/s12881-017-0428-1


BACKGROUND: The thalassemia syndromes are classified according to the globin chain or chains whose production is affected. β-thalassemias are caused by point mutations or, more rarely, deletions or insertions of a few nucleotides in the β-globin gene or its immediate flanking sequences. These mutations interfere with the gene function either at the transcriptional, translational or posttranslational level. METHODS: Two cases of Polish patients with hereditary hemolytic anemia suspected of thalassemia were studied. DNA sequencing and mRNA quantification were performed. Stable human cell lines which express wild-type HBB and mutated versions were used to verify that detected mutation are responsible for mRNA degradation. RESULTS: We identified two different frameshift mutations positioned in the third exon of HBB. Both patients harboring these mutations present the clinical phenotype of thalassemia intermedia and showed dominant pattern of inheritance. In both cases the mutations do not generate premature stop codon. Instead, slightly longer protein with unnatural C-terminus could be produced. Interestingly, although detected mutations are not expected to induce NMD, the mutant version of mRNA is not detectable. Restoring of the open reading frame brought back the RNA to that of the wild-type level. CONCLUSION: Our results show that a lack of natural stop codon due to the frameshift in exon 3 of β-globin gene causes rapid degradation of its mRNA and indicate existence of novel surveillance pathway.

Item Type:Article
Subjects:R Medicine > RZ Other systems of medicine
Divisions:Department of Genetics
ID Code:1354
Deposited By: Dr Beata Burzynska
Deposited On:14 Jun 2017 13:00
Last Modified:14 Jun 2017 13:00

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