title: Molecular analysis of globin gene expression in different thalassaemia disorders: individual variation of β(E) pre-mRNA splicing determine disease severity.
abstract: Thalassaemia is characterized by the reduced or absent production of globins in the haemoglobin molecule leading to imbalanced α-globin/non α-globin chains. HbE, the result of a G to A mutation in codon 26 of the HBB (β-globin) gene, activates a cryptic 5' splice site in codon 25 leading to a reduction of correctly spliced β(E) -globin (HBB:c.79G>A) mRNA and consequently β(+) -thalassaemia. A wide range of clinical severities in bothα- and β-thalassaemia syndromes, from nearly asymptomatic to transfusion-dependent, has been observed. The correlation between clinical heterogeneity in various genotypes of thalassaemia and the levels of globin gene expression and β(E) -globin pre-mRNA splicing were examined using multiplex quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) and allele-specific RT-qPCR. The α-globin/non α-globin mRNA ratio was demonstrated to be a good indicator for disease severity among different thalassaemia disorders. However, the α-globin/non α-globin mRNA ratio ranged widely in β-thalassaemia/HbE patients, with no significant difference between mild and severe phenotypes. Interestingly, the correctly to aberrantly spliced β(E) -globin mRNA ratio in 30% of mild β-thalassaemia/HbE patients was higher than that of the severe patients. The splicing process of β(E) -globin pre-mRNA differs among β-thalassaemia/HbE patients and serves as one of the modifying factors for disease severity.
authors: Thalassemia Research Centre, Institute of Molecular Biosciences, Mahidol University, Nakornpathom, Thailand.
authors: Alisa
authors: A
authors: Tubsuwan
authors: Thongperm
authors: T
authors: Munkongdee
authors: Natee
authors: N
authors: Jearawiriyapaisarn
authors: Chanikarn
authors: C
authors: Boonchoy
authors: Pranee
authors: P
authors: Winichagoon
authors: Suthat
authors: S
authors: Fucharoen
authors: Saovaros
authors: S
authors: Svasti
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005914:Globins / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D011379:Prognosis; D012322:RNA Precursors / Q000235:genetics* / Q000378:metabolism; D012326:RNA Splicing; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D013789:Thalassemia / Q000175:diagnosis / Q000235:genetics*; D055542:alpha-Globins / Q000235:genetics; D055544:beta-Globins / Q000235:genetics
chemical_list: D012322:RNA Precursors; D055542:alpha-Globins; D055544:beta-Globins; D005914:Globins