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

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.

Clinical and Molecular Characteristics of Non-Transfusion-Dependent Thalassemia in Kuwait

“…The present study has confirmed previous findings that the nondeletional a-thal (T Saudi ) is the predominant allele responsible for Hb H disease in the Arabian Peninsula (25,26), which was first described in patients from Saudi Arabia (27,28). Our patients, both the homozygotes and compound heterozygotes for this allele, present with mild-to-moderate anemia, but marked microcytosis and hypochromia.…”

First report of the spectrum of δ‐globin gene mutations in Omani subjects – identification of novel mutations

“…Hemoglobinopathies such as sickle cell anemia, α‐thalassemias, and β‐thalassemias are significantly prevalent in the Sultanate of Oman and represent a major public health issue . Interactions of these disorders among themselves and also with environmental/life style factors, including iron deficiency, generate a wide spectrum of clinical, hematological, and hemoglobin phenotypes.…”