Diversity of beta-globin mutations in Israeli ethnic groups reflects recent historic events.

We characterized nearly 500 beta-thalassemia genes from the Israeli population representing a variety of ethnic subgroups. We found 28 different mutations in the beta-globin gene, including three mutations (beta S, beta C, and beta O-Arab) causing hemoglobinopathies. Marked genetic heterogeneity was observed in both the Arab (20 mutations) and Jewish (17 mutations) populations. On the other hand, two ethnic isolates--Druze and Samaritans--had a single mutation each. Fifteen of the beta-thalassemia alleles are Mediterranean in type, 5 originated in Kurdistan, 2 are of Indian origin, and 2 sporadic alleles came from Europe. Only one mutant allele--nonsense codon 37--appears to be indigenous to Israel. While human habitation in Israel dates back to early prehistory, the present-day spectrum of beta-globin mutations can be largely explained by migration events that occurred in the past millennium.

Severe thalassaemia intermedia caused by interaction of homozygosity for alpha-globin gene triplication with heterozygosity for beta zero-thalassaemia.

A 3-year-old child was evaluated for beta-thalassaemia intermedia. Molecular characterization including beta-globin gene sequence analysis revealed heterozygosity for a single beta-thalassaemia mutation, IVSI nt1 (G-->A). In addition the patient was found to be homozygous for alpha-globin gene triplication (alpha alpha alpha anti3.7/alpha alpha alpah anti3.7). The propositus has a significantly more severe phenotype than has been previously reported with this combination of genetic defects. In contrast, four individuals heterozygous for both triplicated alpha and for beta thalassaemia had a phenotype of thalassaemia minor, and a fifth had very mild thalassaemia intermedia.