Genetic interactions in thalassemia intermedia: Analysis of β-mutations, α-genotype, γ-promoters, and β-LCR hypersensitive sites 2 and 4 in Italian patients

C. Camaschella, U. Mazza, A. Roetto, E. Gottardi, A. Parziale, M. Travi, S. Fattore, D. Bacchiega, G. Fiorelli, M. D. Cappellini

Research output: Contribution to journalArticlepeer-review

Abstract

In order to verify the genetic factors influencing the clinical expression of β-thalassemia we have studied 292 Italian patients, 165 with thalassemia intermedia and 127 with thalassemia major. The β-globin gene mutations were defined in all cases. The number of α-globin genes and the integrity of specific control regions of the β-globin cluster-γ promoters and β-locus Control Region (β-LCR)-were studied in selected cases. Homozygosity for mild mutations (group I) accounts for 24% of the intermedia patients and it is not represented among major patients. Forty-four percent of intermedia patients had combinations of mild/severe (group II) mutations and 32% had homozygosity or double heterozygosity for severe mutations (group III). Seventy-six percent of patients with thalassemia major were classified in group III and 24% in group II. Deletion type -α 3.7 thalassemia, assessed in a part of the cases, was found in 5% of thalassemia major and 19.5% of intermedia patients in groups II and III. Structural analysis of γ promoters and β-LCR HS2 and HS4 regions, carried out in order to look for alterations associated with Hb F increase, did not reveal new mutations. Only rare polymorphic changes were observed at the HS2 and HS4 level. The -158 (G)γC T change was found with an increased incidence in intermedia patients in groups II and III. A subset of 10 β-thalassemia heterozygotes with mild intermedia phenotype resulted from coinheritance of a triplicated α-locus. We have been unable to find a molecular basis for the benign clinical course in approximately 20% of patients with thalassemia intermedia. Other genetic or acquired factors must be hypothesized which ameliorate the clinical condition.

Original languageEnglish
Pages (from-to)82-87
Number of pages6
JournalAmerican Journal of Hematology
Volume48
Issue number2
Publication statusPublished - 1995

Keywords

  • β-globin mutations
  • Fetal hemoglobin
  • Thalassemia intermedia

ASJC Scopus subject areas

  • Hematology

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