title: Role of alternatively spliced beta E-globin mRNA on clinical severity of beta-thalassemia/hemoglobin E disease.
abstract: In spite of seemingly identical genotypes, severity of beta-thalassemia/hemoglobin (Hb) E patients can vary greatly. Some may have a severe clinical disorder approaching that seen in homozygous beta-thalassemia. Since mutation in codon 26 of the beta E-globin gene can lead to an alternative splicing, Hb E acts like a mild beta(+)-thalassemia. Variation in the amount of beta E-globin mRNA may also govern the difference in severity of anemia in beta-thalassemia/Hb E patients who otherwise have the same genetic determinants. We have determined the percentage of the alternatively spliced beta E-globin mRNA by the RT-PCR technique in 14 patients and found that the amount of abnormal spliced beta E-globin mRNA in those patients with severe symptoms ranged between 2.9 to 6.1%, whereas those with milder symptoms had the values which ranged between 1.6 to 2.6%. The extent of beta E-globin mRNA cryptic splicing was better associated with clinical severity of the patients than did the patterns of the Xmn I polymorphism at position -158 of the G gamma-globin gene or levels of Hb F.
authors.affiliation: Department of Medicine, Faculty of Medicine Siriraj Hospital, Institute of Sciences and Technology for Research and Development, Mahidol University, Bangkok, Thailand.
authors.forename: P
authors.initials: P
authors.lastname: Winichagoon
authors.forename: S
authors.initials: S
authors.lastname: Fucharoen
authors.forename: P
authors.initials: P
authors.lastname: Wilairat
authors.forename: K
authors.initials: K
authors.lastname: Chihara
authors.forename: Y
authors.initials: Y
authors.lastname: Fukumaki
mesh_terms: D000293:Adolescent; D000328:Adult; D017398:Alternative Splicing; D001483:Base Sequence; D003062:Codon; D017931:DNA Primers; D005260:Female; D005838:Genotype; D006446:Hemoglobin E / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*; D017086:beta-Thalassemia / Q000235:genetics* / Q000503:physiopathology*
chemical_list: D003062:Codon; D017931:DNA Primers; D012333:RNA, Messenger; D006446:Hemoglobin E