Hb Wilde and Hb Patagonia: Two novel elongated beta-globin variants causing dominant beta-thalassemia

SCHEPS, KAREN G.; HASENAHUER, MARCIA A.; PARISI, GUSTAVO; FORNASARI, MARÍA S.; PENNESI, SANDRA P.; ERRAMOUSPE, BEATRIZ; BASACK, FELISA N.; VEBER, ERNESTO S.; AVERSA, LUIS; ELENA, GRACIELA; VARELA, VIVIANA

EUROPEAN JOURNAL OF HAEMATOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Año: 2015 vol. 94 p. 498 - 503

0902-4441

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 β-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 β-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 β-globins would affect the formation of the αβ dimers and their stability, which would further support the mechanism for the observed clinical features in both patients.