A novel β-globin structural mutant, Hb Brescia (β114 Leu-Pro), causing a severe β-thalassemia intermedia phenotype

✍ Scribed by S. Murru; D. Poddie; G. V. Sciarratta; S. Agosti; M. Baffico; C. Melevendi; M. Pirastu; A. Cao

• Book ID: 102258887
• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 393 KB
• Volume: 1
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/humu.1380010207

✦ Synopsis

This study describes a patient with a thalassemia intermedia-like phenotype in whom P-globin gene sequencing detected a novel abnormal hemoglobin (Hb) due to a T-C substitution at codon 114 of the P-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 P-globin locus. In addition, at-globin gene analysis detected a triple a-globin locus which was inherited from the father.

The T+C change at position 114 of the P-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 neg.

atively with the four alPl contact points of the G-helix most likely adversely affecting the CUP dimer formation. The very severe phenotype presented by our patient is unusual in a heterozygote for an unstable H b variant and may be explained by the coinheritance of the triple a-globin locus.