A novel beta-globin structural mutant, Hb Brescia (beta 114 Leu-Pro), causing a severe beta-thalassemia intermedia phenotype.

Abstract

This study describes a patient with a thalassemia intermedia-like phenotype in whom beta-globin gene sequencing detected a novel abnormal hemoglobin (Hb) due to a T-C substitution at codon 114 of the beta-globin gene arising as a de novo mutation. The abnormal variant was designated Hb Brescia after the place of birth of the propositus. Normal sequences were detected at the in trans beta-globin locus. In addition, alpha-globin gene analysis detected a triple alpha-globin locus which was inherited from the father. The T-C change at position 114 of the beta-globin gene results in a leucine to proline substitution (Leu-Pro) in the G-helix. The resulting Hb tetramer is highly unstable and precipitates forming inclusion bodies in the peripheral red blood cells. Moreover, the Leu-Pro substitution interferes negatively with the four alpha 1 beta 1 contact points of the G-helix most likely adversely affecting the alpha beta dimer formation. The very severe phenotype presented by our patient is unusual in a heterozygote for an unstable Hb variant and may be explained by the coinheritance of the triple alpha-globin locus.

• Authors: S Murru, D Poddie, G V Sciarratta, S Agosti, M Baffico, C Melevendi, M Pirastu, A Cao
• Journal: Human mutation (Hum Mutat) Vol. 1 Issue 2 Pg. 124-8 ( 1992) ISSN: 1059-7794 [Print] United States
• PMID: 1301199 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hemoglobins, Abnormal
• Macromolecular Substances
• hemoglobin Brescia
• Globins
• Proline
• Leucine

Topics

• Adolescent
• Base Sequence
• Erythrocytes (physiology)
• Female
• Globins (genetics)
• Hemoglobins, Abnormal (genetics)
• Humans
• Italy
• Leucine
• Macromolecular Substances
• Male
• Molecular Sequence Data
• Proline
• beta-Thalassemia (blood, genetics)