title: Interaction of two different disorders in the beta-globin gene cluster associated with an increased hemoglobin F production: a novel deletion type of (G) gamma + ((A) gamma delta beta)(0)-thalassemia and a delta(0)-hereditary persistence of fetal hemoglobin determinant.
abstract: We report two different disorders of the beta-globin gene cluster segregating in a Belgian family: a novel deletion that results in (G) gamma + ((A) gamma delta beta)(0)-thalassemia (thal) and a heterocellular hereditary persistence of foetal hemoglobin of the Swiss type linked to a delta(0)-thal gene (delta (0)-HPFH). Heterozygosity for the heterocellular HPFH brings about a moderate (3.4% to 8.24%) increase of hemoglobin (Hb) F having a G gamma/A gamma ratio of 4:1, whereas carriers of the G gamma + ((A) gamma delta beta)(0)-thal deletion show in their peripheral blood a considerably higher (15%) percentage of Hb F. Both defects interact in the compound heterozygotes for G gamma + ((A) gamma delta beta)(0)-thal and delta(0)-HPFH producing a further increase (up to 24%) of fetal Hb consisting entirely of G gamma chains. Molecular characterization of the (G) gamma + ((A) gamma delta beta)(0)-thal by means of Southern analysis showed that the deletion spans about 50 kb, removing the 3' end of the A gamma-gene, the psi beta-, delta-, and beta-genes. A number of possible mechanisms leading to the overproduction of Hb F in HPFH and (G) gamma + ((A) gamma delta beta)(0)-thal will be discussed.
authors.affiliation: Department of Human Genetics, State University, Sylvius Laboratory, Leiden, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Losekoot
authors.forename: R
authors.initials: R
authors.lastname: Fodde
authors.forename: E J
authors.initials: EJ
authors.lastname: Gerritsen
authors.forename: I
authors.initials: I
authors.lastname: van de Kuit
authors.forename: A
authors.initials: A
authors.lastname: Schreuder
authors.forename: P C
authors.initials: PC
authors.lastname: Giordano
authors.forename: J M
authors.initials: JM
authors.lastname: Vossen
authors.forename: L F
authors.initials: LF
authors.lastname: Bernini
mesh_terms: D000328:Adult; D002675:Child, Preschool; D002872:Chromosome Deletion; D004909:Erythrocyte Indices; D005260:Female; D005319:Fetal Hemoglobin / Q000096:biosynthesis / Q000235:genetics*; D005914:Globins / Q000235:genetics*; D006453:Hemoglobinopathies / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D010375:Pedigree; D015183:Restriction Mapping; D013789:Thalassemia / Q000097:blood / Q000235:genetics*
chemical_list: D005914:Globins; D005319:Fetal Hemoglobin