title: 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.
authors.affiliation: Department of Child Health, Sultan Qaboos University, Muscat, Oman.
authors.forename: Yasser
authors.initials: Y
authors.lastname: Wali
authors.forename: Shoaib Al
authors.initials: SA
authors.lastname: Zadjali
authors.forename: Mohamed
authors.initials: M
authors.lastname: Elshinawy
authors.forename: Ismail
authors.initials: I
authors.lastname: Beshlawi
authors.forename: Naglaa
authors.initials: N
authors.lastname: Fawaz
authors.forename: Salam
authors.initials: S
authors.lastname: Alkindi
authors.forename: Abdulhakim
authors.initials: A
authors.lastname: Rawas
authors.forename: Siham
authors.initials: S
authors.lastname: Alsinani
authors.forename: Shahina
authors.initials: S
authors.lastname: Daar
authors.forename: Rajagopal
authors.initials: R
authors.lastname: Krishnamoorthy
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D017353:Gene Deletion; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009850:Oman; D010375:Pedigree; D017354:Point Mutation; D055542:alpha-Globins / Q000235:genetics*; D017085:alpha-Thalassemia / Q000097:blood / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D055542:alpha-Globins