Molecular comparison of δβ-thalassemia and hereditary persistence of fetal hemoglobin DNAs: Evidence of a regulatory area?

S. Ottolenghi, B. Giglioni, R. Taramelli, P. Comi, U. Mazza, G. Saglio, C. Camaschella, P. Izzo, A. Cao, R. Galanello, E. Gimferrer, M. Baiget, A. M. Gianni

Research output: Contribution to journalArticlepeer-review

Abstract

The hematological phenotypes of several Mediterranean patients with δβ-thalassemia and hereditary persistence of fetal hemoglobin have been characterized. Although clinical and hematological characteristics are essentially superimposable in all heterozygous δβ-thalassemics, these patients show typical Gγ/Aγ ratios in their Hb F, ranging from ≃ 0.07 in Sardinian to ≃0.15 in Sicilian and ≃0.35 in Spanish patients. Aγ (Sardinian)-(isoleucine-75 → threonine) is found in Spanish patients and accounts for all of the Aγ production in heterozygotes, indicating that persistent production of γ chains occurs cis to the δβ-thalassemia gene. The molecular heterogeneity of these conditions is demonstrated by restriction enzyme mapping of DNA; Sicilian and Calabrian patients show a deletion starting from the δ-globin intron and extending several kilobases 3' to the β-globin gene; in Spanish patients the deletion starts ≃ 2-3 kilobases 5' to the δ-globin gene and extends well beyond the β-globin gene. Comparison of these deletions with previously described ones in Negro and in a new Southern Italian case of hereditary persistence of fetal hemoglobin suggests that the deletion of a region centered at a cluster of repetitive sequences ≃ 3.5 kilobases 5' to the δ-globin gene may be critical for the persistent expression of high levels of γ-globin in hereditary persistence of fetal hemoglobin compared to δβ-thalassemia. The concept that the deletion or mutation of specific areas (rather than nonspecific changes brought about by large deletions in the globin cluster) is important in determining the persistent expression of γ-globin genes is supported by the finding of a nondeletion type of δβ-thalassemia in Sardinians.

Original languageEnglish
Pages (from-to)2347-2351
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume79
Issue number7 I
Publication statusPublished - 1982

ASJC Scopus subject areas

  • Genetics
  • General

Fingerprint

Dive into the research topics of 'Molecular comparison of δβ-thalassemia and hereditary persistence of fetal hemoglobin DNAs: Evidence of a regulatory area?'. Together they form a unique fingerprint.

Cite this