Italian type of deletional hereditary persistence of fetal hemoglobin

Abstract

We report a new type of deletion of the ß globin gene cluster in the Italian population that confers a phenotype of hereditary persistence of fetal hemoglobin (HPFH) to the carriers. This deletion begins ~5 kilobases (kb) 5' to the d globin gene and ends ~30 kb 3' to the ß globin gene, in close proximity to the 3' end of an Indian HPFH. In all four previously described HPFH, a repetitive Alu I region 5' to the d globin gene is largely or completely deleted; the 5' end of the new HPFH is consistent with this common feature. In addition, the finding that Italian and Indian HPFHs, as reported for other groups of deletions, have very close 3' ends, strengthens the idea that common mechanisms may operate in generating these deletions. Finally, we show that, in spite of similar 5' breakpoints, the deletion of Spanish dß°-thalassemia is at least 8 kb longer than that of Negro HPFH type I, thus ruling out the hypothesis that the overall extent of the deletion might influence the level of ? globin chain synthesis.