Abstract

Several factors influence the severity of homozygous β-thalassemia: β-thalassemia intermedia (non-transfusion dependent) patients often have at least one β⁺-thalassemia allele with only moderate impairment of β-globin production. β-thalassemia is also ameliorated by coinheritance of α-thalassemia or by γ-globin promoter mutations, such as T at position -158, which increase fetal hemoglobin production.
In Sardinia, the codon 39 nonsense mutation (β39) is the primary cause of Β⁰-thalassemia. Two-thirds of northern Sardinian patients have this mutation on haplotype II, while one-fourth have it on haplotype I. Haplotype II, with ++ at the Hind III sites in the ^Gγ and ^Aγ genes, is strongly associated with the variant ^Aγ^T globin, while haplotype I is associated with the normal ^Aγ^I.
We have previously demonstrated that a β⁰-thalassemia haplotype found in a black family, with ++ at the Hind III sites, had a 4-base-pair (bp) deletion at positions -225 to -222 of the ^Aγ gene, in association with reduced ^Aγ (elevated ^Sγ ) levels. We have now extended this study to northern Sardinia, providing statistical data for the association of the 4-bp deletion with decreased ^Aγ^T expression.

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