Biochemical and molecular aspects of beta-thalassemia types in northern Sardinia.

Forty-three patients with beta-thalassemia from Northern Sardinia (31 severe and polytransfused, six follow-up babies, five adults with mild thalassemia who were not transfusion dependent, and a young transfused patient was also affected by a disease of intermediate severity) were studied in order to establish the fetal hemoglobin composition, restriction fragment length polymorphism haplotypes at the beta-globin gene cluster, and the type(s) of mutation. Haplotype II was prevalent, [56/86 chromosomes (65%)], haplotype I was also fairly common, [22/86 chromosomes (25%)], while other types were relatively rare. The nonsense mutation at codon 39 was nearly exclusive, [76/80 chromosomes (95%)]. Other beta-thalassemia mutations occurred on chromosomes with haplotypes III, IX, X, and perhaps V, and a new type related to II. The mutated A gamma T gene was associated with type II, X, and the new type. Type IX was linked to a beta(0) gene and to an Xmn I site 5' to the G gamma gene, to a high G gamma globin level, and to a disease of mild severity. Type III was associated with a beta(+)-thalassemic gene. The (0)39 mutation linked to type II was associated with thalassemia intermedia in three patients.