title: The role of heterocellular hereditary persistence of fetal haemoglobin in beta(0)-thalassaemia intermedia.
abstract: Beta(0)-thalassaemia intermedia (beta(0)-TI) describes patients who lack beta-globin synthesis yet manifest a non-transfusion-dependent form of beta-thalassaemia. Co-inheritance of alpha-thalassaemia, certain variants of the beta-like globin gene cluster and elevated fetal haemoglobin (HbF) production are all associated with beta(0)-TI. However, the mild phenotypes of many beta(0)-TI patients are unexplained. Genetically determined HbF levels in beta-thalassaemia are difficult to assess because erythrocytes containing HbF (F cells) preferentially survive over erythrocytes without HbF. To evaluate the importance of genetically elevated HbF in beta-thalassaemia, F-cell levels of 19 TI patients' relatives were compared with relatives of transfusion-dependent beta-thalassaemia major patients and those of beta-globin genotype-matched controls. The beta-globin and alpha-globin genotypes, as well as their Ggamma promoter were also examined. Using this approach, in all but one patient the mild phenotype was attributable to either alpha-globin genotype, gamma-globin promoter polymorphism or inherited elevated F-cell levels. The findings of this study establish the F-cell levels required to modify the degree of disease severity significantly and demonstrate that F-cell level is a crucial parameter in the understanding of phenotypic variation in beta-thalassaemia.
authors.affiliation: Division of Medical Genetics, Department of Internal Medical Science, University of Cagliari, Via Is Guadazzonis, 09100 Cagliari, Italy. christy.chang@tiscalinet.it
authors.forename: Y P
authors.initials: YP
authors.lastname: Chang
authors.forename: R
authors.initials: R
authors.lastname: Littera
authors.forename: R
authors.initials: R
authors.lastname: Garau
authors.forename: K D
authors.initials: KD
authors.lastname: Smith
authors.forename: G J
authors.initials: GJ
authors.lastname: Dover
authors.forename: S
authors.initials: S
authors.lastname: Iannelli
authors.forename: E
authors.initials: E
authors.lastname: Cacace
authors.forename: L
authors.initials: L
authors.lastname: Contu
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004906:Erythrocyte Count; D004912:Erythrocytes / Q000378:metabolism*; D005319:Fetal Hemoglobin / Q000032:analysis* / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D005914:Globins / Q000235:genetics; D006801:Humans; D007558:Italy; D009154:Mutation; D017086:beta-Thalassemia / Q000097:blood* / Q000235:genetics*
chemical_list: D005914:Globins; D005319:Fetal Hemoglobin