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

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

EUROPEAN JOURNAL OF HAEMATOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2014 vol. 93 p. 1 - 6

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 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.