Skip to main content
PMC home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1986 Nov;39(5):631–639.

Molecular basis for HbH disease in Italy: geographical distribution of deletional and nondeletional alpha-thalassemia haplotypes.

A Di Rienzo, A Novelletto, M C Aliquò, I Bianco, A Tagarelli, C Brancati, B Colombo, L Felicetti
PMCID: PMC1684059  PMID: 2878610

Abstract

We have investigated the molecular basis for HbH disease in 16 patients from Sardinia, and central and southern Italy. We have shown that HbH disease is produced by the interaction of at least 10 different deletional or nondeletional alpha-thalassemia haplotypes, some of which have been already described in the Mediterranean area (--Med,-(alpha)20.5,-alpha 3.7 type I,-alpha 3.7 type II, alpha 2 NcoI alpha 1, alpha 2 HphI alpha 1). Among the new mutations found in the course of our study, there is a complete deletion of the zeta-alpha cluster and three nondeletional determinants (alpha alpha T), affecting to various extents alpha-globin gene expression. The different alpha-thalassemia haplotypes are not evenly distributed throughout the country. Two alpha 0 determinants [-(alpha)20.5 and the complete deletion of the zeta-alpha cluster] and four alpha + determinants (-alpha 3.7 type II, three nondeletional alpha alpha T mutations) are found exclusively in southern Italy.

Full text

PDF
635

Images in this article

634Fig. 2
on p.634
636Fig. 3
on p.636

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bianco I., Graziani B., Lerone M., Congedo P., Ponzini D., Braconi F., Aliquo C. A screening programme for the prospective prevention of Mediterranean anaemia in Latium: results of seven years' work. J Med Genet. 1984 Aug;21(4):268–271. doi: 10.1136/jmg.21.4.268. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Deisseroth A., Nienhuis A., Turner P., Velez R., Anderson W. F., Ruddle F., Lawrence J., Creagan R., Kucherlapati R. Localization of the human alpha-globin structural gene to chromosome 16 in somatic cell hybrids by molecular hybridization assay. Cell. 1977 Sep;12(1):205–218. doi: 10.1016/0092-8674(77)90198-2. [DOI] [PubMed] [Google Scholar]
  3. Di Rienzo A., Felicetti L., Novelletto A., Forteleoni G., Colombo B. Frequency and types of deletional alpha+-thalassemia in northern Sardinia. Hum Genet. 1985;71(2):147–149. doi: 10.1007/BF00283371. [DOI] [PubMed] [Google Scholar]
  4. Felice A. E., Cleek M. P., McKie K., McKie V., Huisman T. H. The rare alpha-thalassemia-1 of blacks is a zeta alpha-thalassemia-1 associated with deletion of all alpha- and zeta-globin genes. Blood. 1984 May;63(5):1253–1257. [PubMed] [Google Scholar]
  5. Galanello R., Maccioni L., Ruggeri R., Perseu L., Cao A. Alpha thalassaemia in Sardinian newborns. Br J Haematol. 1984 Oct;58(2):361–368. doi: 10.1111/j.1365-2141.1984.tb06095.x. [DOI] [PubMed] [Google Scholar]
  6. Higgs D. R., Goodbourn S. E., Lamb J., Clegg J. B., Weatherall D. J., Proudfoot N. J. Alpha-thalassaemia caused by a polyadenylation signal mutation. Nature. 1983 Nov 24;306(5941):398–400. doi: 10.1038/306398a0. [DOI] [PubMed] [Google Scholar]
  7. Higgs D. R., Hill A. V., Bowden D. K., Weatherall D. J., Clegg J. B. Independent recombination events between the duplicated human alpha globin genes; implications for their concerted evolution. Nucleic Acids Res. 1984 Sep 25;12(18):6965–6977. doi: 10.1093/nar/12.18.6965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Higgs D. R., Weatherall D. J. Alpha-thalassemia. Curr Top Hematol. 1983;4:37–97. [PubMed] [Google Scholar]
  9. Lauer J., Shen C. K., Maniatis T. The chromosomal arrangement of human alpha-like globin genes: sequence homology and alpha-globin gene deletions. Cell. 1980 May;20(1):119–130. doi: 10.1016/0092-8674(80)90240-8. [DOI] [PubMed] [Google Scholar]
  10. Morlé F., Lopez B., Henni T., Godet J. alpha-Thalassaemia associated with the deletion of two nucleotides at position -2 and -3 preceding the AUG codon. EMBO J. 1985 May;4(5):1245–1250. doi: 10.1002/j.1460-2075.1985.tb03767.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Nicholls R. D., Higgs D. R., Clegg J. B., Weatherall D. J. Alpha zero-thalassemia due to recombination between the alpha 1-globin gene and an AluI repeat. Blood. 1985 Jun;65(6):1434–1438. [PubMed] [Google Scholar]
  12. Orkin S. H., Goff S. C., Hechtman R. L. Mutation in an intervening sequence splice junction in man. Proc Natl Acad Sci U S A. 1981 Aug;78(8):5041–5045. doi: 10.1073/pnas.78.8.5041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Orkin S. H., Michelson A. Partial deletion of the alpha-globin structural gene in human alpha-thalassaemia. Nature. 1980 Jul 31;286(5772):538–540. doi: 10.1038/286538a0. [DOI] [PubMed] [Google Scholar]
  14. Orkin S. H., Old J., Lazarus H., Altay C., Gurgey A., Weatherall D. J., Nathan D. G. The molecular basis of alpha-thalassemias: frequent occurrence of dysfunctional alpha loci among non-Asians with Hb H disease. Cell. 1979 May;17(1):33–42. doi: 10.1016/0092-8674(79)90292-7. [DOI] [PubMed] [Google Scholar]
  15. Pirastu M., Lee K. Y., Dozy A. M., Kan Y. W., Stamatoyannopoulos G., Hadjiminas M. G., Zachariades Z., Angius A., Furbetta M., Rosatelli C. Alpha-thalassemia in two Mediterranean populations. Blood. 1982 Aug;60(2):509–512. [PubMed] [Google Scholar]
  16. Pirastu M., Saglio G., Chang J. C., Cao A., Kan Y. W. Initiation codon mutation as a cause of alpha thalassemia. J Biol Chem. 1984 Oct 25;259(20):12315–12317. [PubMed] [Google Scholar]
  17. Proudfoot N. J., Maniatis T. The structure of a human alpha-globin pseudogene and its relationship to alpha-globin gene duplication. Cell. 1980 Sep;21(2):537–544. doi: 10.1016/0092-8674(80)90491-2. [DOI] [PubMed] [Google Scholar]
  18. Weatherall D. J., Higgs D. R., Bunch C., Old J. M., Hunt D. M., Pressley L., Clegg J. B., Bethlenfalvay N. C., Sjolin S., Koler R. D. Hemoglobin H disease and mental retardation: a new syndrome or a remarkable coincidence? N Engl J Med. 1981 Sep 10;305(11):607–612. doi: 10.1056/NEJM198109103051103. [DOI] [PubMed] [Google Scholar]
  19. Winichagoon P., Higgs D. R., Goodbourn S. E., Clegg J. B., Weatherall D. J., Wasi P. The molecular basis of alpha-thalassaemia in Thailand. EMBO J. 1984 Aug;3(8):1813–1818. doi: 10.1002/j.1460-2075.1984.tb02051.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES