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Severity ranking of non‐deletional alpha thalassemic alleles: insights from an Omani family study
Author(s) -
Wali Yasser,
Zadjali Shoaib Al,
Elshinawy Mohamed,
Beshlawi Ismail,
Fawaz Naglaa,
AlKindi Salam,
Rawas Abdulhakim,
Alsinani Siham,
Daar Shahina,
Krishnamoorthy Rajagopal
Publication year - 2011
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.2011.01606.x
Subject(s) - genetics , allele , biology , mutation , hemolysis , thalassemia , gene , phenotype , alpha thalassemia , microbiology and biotechnology , genotype , immunology
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.