Hb Wilde and Hb Patagonia: two novel elongated beta-globin variants causing dominant beta-thalassemia
We describe here the molecular and hematological characteristics of novel frameshift mutations in exon 2 of the HBB gene (in heterozygous state) found in two Argentinean pediatric patients with dominant b-thalassemia-like features. In Hb Wilde, HBB:c.270_273delTGAG(p.Glu90Cysfs*67), we detected the...
| Autores: | , , , , , , , , , , |
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| Formato: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2014 |
| País: | Argentina |
| Recursos: | Consejo Nacional de Investigaciones Científicas y Técnicas |
| Repositorio: | CONICET Digital (CONICET) |
| Idioma: | inglés |
| OAI Identifier: | oai:ri.conicet.gov.ar:11336/105265 |
| Acesso em linha: | http://hdl.handle.net/11336/105265 |
| Access Level: | acceso abierto |
| Palavra-chave: | elongated beta-globin protein structure dominant beta-thalassemia frameshift mutations https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 https://purl.org/becyt/ford/3.3 https://purl.org/becyt/ford/3 https://purl.org/becyt/ford/1.2 |
| Resumo: | We describe here the molecular and hematological characteristics of novel frameshift mutations in exon 2 of the HBB gene (in heterozygous state) found in two Argentinean pediatric patients with dominant b-thalassemia-like features. In Hb Wilde, HBB:c.270_273delTGAG(p.Glu90Cysfs*67), we detected the deletion of the third base of the codon 89 (T) and the codon 90 (GAG), whereas in Hb Patagonia, HBB: c.296_297dupGT(p.Asp99Trpfs*59), the frameshift mutation was due to a duplication of a ‘GT’ dinucleotide after the second base of codon 98 (GTG). The Hb Patagonia and Hb Wilde mutations would result in elongated b-globin chains with modified C-terminal sequences and a total of 155 and 157 amino acids residues, respectively. Based on bioinformatics and structural analysis, as well as protein modeling, we predict that the elongated b-globins would affect the formation of the ab dimers and their stability, which would further support the mechanism for the observed clinical features in both patients. |
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