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 (-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.
AB - 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.
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
VL - 86
SP - 507
EP - 511
JO - European Journal of Haematology
JF - European Journal of Haematology
SN - 0902-4441
IS - 6
ER -