Molecular and structural characterization of a novel β-hemoglobinopathy caused by in Cis β-globin mutations in a Thai individual
Issued Date
2025-12-01
Resource Type
eISSN
20452322
Scopus ID
2-s2.0-105022522802
Pubmed ID
41266470
Journal Title
Scientific Reports
Volume
15
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Scientific Reports Vol.15 No.1 (2025)
Suggested Citation
Singha K., Pansuwan A., Sanachai K., Nutho B., Fucharoen G., Fucharoen S. Molecular and structural characterization of a novel β-hemoglobinopathy caused by in Cis β-globin mutations in a Thai individual. Scientific Reports Vol.15 No.1 (2025). doi:10.1038/s41598-025-24941-5 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/113276
Title
Molecular and structural characterization of a novel β-hemoglobinopathy caused by in Cis β-globin mutations in a Thai individual
Corresponding Author(s)
Other Contributor(s)
Abstract
Hemoglobin (Hb) E is the most common Hb variant in Southeast Asia. We described a novel form of Hb E caused by an in cis combination of Hb E and another β-hemoglobinopathy affecting Hb stability. Study was done on a Thai woman at a routine prenatal screening of thalassemia. Hb analysis was carried out by HPLC and capillary electrophoresis. Mutation and β-globin gene haplotype analyses were done using PCR-based assays. Structure of the abnormal Hb molecule was predicted using molecular dynamics simulations. The subject had mild normocytic anemia with Hb 10.3 g/dL. Hb-HPLC analysis revealed Hb A<inf>2</inf>A with 6.9% Hb A<inf>2</inf>, whereas capillary electrophoresis showed Hb A<inf>2</inf>EA with 3.6% Hb A<inf>2</inf> and 3.4% Hb E. No α- and β-thalassemia mutations were detected. Further β-globin gene analysis identified a novel variant caused by two in cis mutations, i.e., Hb E (codon 26 GAG > AAG) and Hb Palmerston North (codon 23 GTT > TTT), namely Hb E-Hb Palmerston North. Splicing site prediction of the Hb E-Palmerston North gene showed similar splicing scores at both normal and cryptic splice sites with those of the Hb E gene. System stability prediction of the Hb E-Palmerston North expression indicated a weakening αβ contact, resulting in instability and a dramatic reduction of Hb variant (3.4%). The novel Hb E variant, designated Hb E-Palmerston North, was characterized by unusually low levels, which was attributed to its high instability. The diagnosis of this novel Hb variant is best by multiplex PCR assay developed.