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 language | English |
|---|---|
| Pages (from-to) | 507-511 |
| Number of pages | 5 |
| Journal | European Journal of Haematology |
| Volume | 86 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 2011 |
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Keywords
- Alleles
- Alpha thalassemia
- Genetics
- Non-deletional mutations
ASJC Scopus subject areas
- Hematology
Cite this
Severity ranking of non-deletional alpha thalassemic alleles : Insights from an Omani family study. / Wali, Yasser; Zadjali, Shoaib Al; Elshinawy, Mohamed; Beshlawi, Ismail; Fawaz, Naglaa; Alkindi, Salam; Rawas, Abdulhakim; Alsinani, Siham; Daar, Shahina; Krishnamoorthy, Rajagopal.
In: European Journal of Haematology, Vol. 86, No. 6, 06.2011, p. 507-511.Research output: Contribution to journal › Article
}
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
UR - http://www.scopus.com/inward/citedby.url?scp=79956003658&partnerID=8YFLogxK
U2 - 10.1111/j.1600-0609.2011.01606.x
DO - 10.1111/j.1600-0609.2011.01606.x
M3 - Article
VL - 86
SP - 507
EP - 511
JO - European Journal of Haematology
JF - European Journal of Haematology
SN - 0902-4441
IS - 6
ER -