Two novel unstable hemoglobin variants due to in-frame deletions of key amino acids in the β-globin chain.

Abstract:

:Hemoglobinopathies are the most common autosomal recessive disorders and are mostly inherited in a recessive manner. However, certain mutations can affect the globin chain stability, leading to dominant forms of thalassemia. The aim of this work was the molecular and structural characterization of two heterozygous in-frame deletions, leading to β-globin variants in pediatric patients in Argentina. The HBB gene of the probands and their parents was sequenced, and other markers of globin chain imbalance were analyzed. Several structural analyses were performed, and the effect of the mutations on the globin chain stability was analyzed. In Hb JC-Paz, HBB:c.29_37delCTGCCGTTA (p.Ala10_Thr12del), detected in an Argentinean boy, one α-helix turn is expected to be lost. In Hb Tavapy, HBB:c.182_187delTGAAGG (p.Val60_Lys61del), the deleted residues are close to distal histidine (His63) in the heme pocket. Both mutations are predicted to have a destabilizing effect. The development of computational structural models and bioinformatics algorithms is expected to become a useful tool to understand the impact of the mutations leading to dominant thalassemia.

journal_name

Eur J Haematol

authors

Scheps KG,Hasenahuer MA,Parisi G,Targovnik HM,García E,Veber ES,Crisp R,Elena G,Varela V,Fornasari MS

doi

10.1111/ejh.13029

subject

Has Abstract

pub_date

2018-06-01 00:00:00

pages

529-535

issue

6

eissn

0902-4441

issn

1600-0609

journal_volume

100

pub_type

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