Severity ranking of non-deletional alpha thalassemic alleles: Insights from an Omani family study

Yasser Wali, Shoaib Al Zadjali, Mohamed Elshinawy, Ismail Beshlawi, Naglaa Fawaz, Salam Alkindi, Abdulhakim Rawas, Siham Alsinani, Shahina Daar, Rajagopal Krishnamoorthy

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

In an Omani family, four different alpha thalassemic alleles, one single-gene deletional (-α 3.7) and three non-deletional forms (α TSaudi, α Δ5nt, and α ΔG), interact in various combinations and result in two distinct hematological phenotypes, with and without HbH inclusions. After excluding the presence of potential genetic modifiers, viz associated β-thalassemic alleles or functional alpha hemoglobin stabilizing protein (AHSP) polymorphisms, we observed that only the genetic combinations involving α TSaudi mutation are associated with HbH inclusions (a marker of degree of α/β-chain imbalance) and high reticulocyte count (a marker of ongoing hemolysis). Overall, the α TSaudi mutation is associated with a more severe α-globin deficiency than the other two (α Δ5nt and α ΔG) non-deletional α 0 thalassemic mutations. The likely molecular explanation is that the compensatory increase in the linked α1 globin gene expression is much more compromised in cases with α TSaudi mutation.

Original languageEnglish
Pages (from-to)507-511
Number of pages5
JournalEuropean Journal of Haematology
Volume86
Issue number6
DOIs
Publication statusPublished - Jun 2011

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Keywords

  • Alleles
  • Alpha thalassemia
  • Genetics
  • Non-deletional mutations

ASJC Scopus subject areas

  • Hematology

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