Abstract

In Sardinia, the β-39 nonsense mutation is the primary cause of β⁰-thalassaemia. This mutation is found mainly on β-globin gene cluster haplotypes I and II, which differ in their ^Aγ globin types (^Aγ^I and ^Aγ^T, respectively). This report presents data on ^Gγ, ^Aγ^I and ^Aγ^T levels, and the presence or absence of a 4 base pair (bp) deletion at -225 to -222 of the ^Aγ globin promoter, in 55 poly-transfused β⁰-thalassaemia major patients. Six patients were homozygotes for the normal (N) ^Aγ promoter lacking the 4 bp deletion, had no ^Aγ^T globin, and their mean ^Gγ:^Aγ^I:^Aγ^T ratio was 52•9:47•1:0. Twenty-five patients were homozygotes for the mutant (M) ^Aγ promoter with the 4 bp deletion, had no ^Aγ^I globin, and the mean ^Gγ:^Aγ^I:^Aγ^T ratio was 62•1:0:37•9. For M/M compared to N/N, the lower ^Aγ^T than ^Aγ^I was significant by the t-test (P<0•001). Twenty-four N/M cases had mean ^Gγ:^Aγ^I:^Aγ^T of 56:24•4:19•6, and the lower ^Aγ^T than ^Aγ^I was also significant (P<0•001). Partial haplotype analysis on these and 17 other β⁰-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 ^Aγ^T globin gene on haplotype II.

I documenti depositati in UnissResearch sono protetti dalle leggi che regolano il diritto d'autore