title: Diminished A gamma T fetal globin levels in Sardinian haplotype II beta 0-thalassaemia patients are associated with a four base pair deletion in the A gamma T promoter.
abstract: In Sardinia, the beta-39 nonsense mutation is the primary cause of beta 0-thalassaemia. This mutation is found mainly on beta-globin gene cluster haplotypes I and II, which differ in their A gamma globin types (A gamma I and A gamma T, respectively). This report presents data on G gamma, A gamma I and A gamma T levels, and the presence or absence of a 4 base pair (bp) deletion at -225 to -222 of the A gamma globin promoter, in 55 poly-transfused beta 0-thalassaemia major patients. Six patients were homozygotes for the normal (N) A gamma promoter lacking the 4 bp deletion, had no A gamma T globin, and their mean G gamma:A gamma I: A gamma T ratio was 52.9:47.1:0. Twenty-five patients were homozygotes for the mutant (M) A gamma promoter with the 4 bp deletion, had no A gamma I globin, and the mean G gamma:A gamma I: A gamma T ratio was 62.1:0:37.9. For M/M compared to N/N, the lower A gamma T than A gamma I was significant by the t-test (P less than 0.001). Twenty-four N/M cases had mean G gamma:A gamma I:A gamma T of 56:24.4:19.6, and the lower A gamma T than A gamma I was also significant (P less than 0.001). Partial haplotype analysis on these and 17 other beta 0-thalassaemia patients suggested that the 4 bp deletion was strongly associated with haplotype II. Of 33 M/M, 32 were haplotype II/II and one was II/5a; of 31 N/M, 29 were I/II and two were II/IX; of eight N/N, seven were haplotype I/I and one was I/IX. These data show a strong association of the 4 bp promoter deletion with decreased expression of the A gamma T globin gene on haplotype II.
authors.affiliation: Institute of General Physiology and Biological Chemistry, University of Sassari, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Manca
authors.forename: E
authors.initials: E
authors.lastname: Cocco
authors.forename: D
authors.initials: D
authors.lastname: Gallisai
authors.forename: B
authors.initials: B
authors.lastname: Masala
authors.forename: J G
authors.initials: JG
authors.lastname: Gilman
mesh_terms: D001483:Base Sequence; D002872:Chromosome Deletion; D004247:DNA / Q000032:analysis*; D005319:Fetal Hemoglobin / Q000235:genetics*; D005914:Globins / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007558:Italy; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013789:Thalassemia / Q000235:genetics*
chemical_list: D005914:Globins; D004247:DNA; D005319:Fetal Hemoglobin