Scholarlink

<p>Hemoglobin (Hb) E is the most common Hb variant in Southeast Asia. We described a novel form of Hb E caused by an <i>in cis</i> 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&#xa0;g/dL. Hb-HPLC analysis revealed Hb A<sub>2</sub>A with 6.9% Hb A<sub>2</sub>, whereas capillary electrophoresis showed Hb A<sub>2</sub>EA with 3.6% Hb A<sub>2</sub> 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 <i>in cis</i> mutations, i.e., Hb E (codon 26 GAG &gt; AAG) and Hb Palmerston North (codon 23 GTT &gt; 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Molecular and structural characterization of a novel β-hemoglobinopathy caused by in Cis β-globin mutations in a Thai individual

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月20日

查看全文
  • Kritsada Singha,
  • Anupong Pansuwan,
  • Kamonpan Sanachai,
  • Bodee Nutho,
  • Goonnapa Fucharoen,
  • Supan Fucharoen

摘要

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 A2A with 6.9% Hb A2, whereas capillary electrophoresis showed Hb A2EA with 3.6% Hb A2 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.