TY - JOUR
T1 - Severity ranking of non-deletional alpha thalassemic alleles
T2 - Insights from an Omani family study
AU - Wali, Yasser
AU - Zadjali, Shoaib Al
AU - Elshinawy, Mohamed
AU - Beshlawi, Ismail
AU - Fawaz, Naglaa
AU - Alkindi, Salam
AU - Rawas, Abdulhakim
AU - Alsinani, Siham
AU - Daar, Shahina
AU - Krishnamoorthy, Rajagopal
PY - 2011/6
Y1 - 2011/6
N2 - In an Omani family, four different alpha thalassemic alleles, one single-gene deletional (-α3.7) and three non-deletional forms (αTSaudi, αΔ5nt, and αΔG), 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 αTSaudi 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 αTSaudi mutation is associated with a more severe α-globin deficiency than the other two (αΔ5nt and αΔG) non-deletional α0 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 αTSaudi mutation.
AB - In an Omani family, four different alpha thalassemic alleles, one single-gene deletional (-α3.7) and three non-deletional forms (αTSaudi, αΔ5nt, and αΔG), 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 αTSaudi 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 αTSaudi mutation is associated with a more severe α-globin deficiency than the other two (αΔ5nt and αΔG) non-deletional α0 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 αTSaudi mutation.
KW - Alleles
KW - Alpha thalassemia
KW - Genetics
KW - Non-deletional mutations
UR - http://www.scopus.com/inward/record.url?scp=79956003658&partnerID=8YFLogxK
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U2 - 10.1111/j.1600-0609.2011.01606.x
DO - 10.1111/j.1600-0609.2011.01606.x
M3 - Article
C2 - 21410534
AN - SCOPUS:79956003658
SN - 0902-4441
VL - 86
SP - 507
EP - 511
JO - European Journal of Haematology
JF - European Journal of Haematology
IS - 6
ER -