Biochemical and molecular aspects of βthalassemia types in northern sardinia

Forty-three patients with βthalassemia 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 1ength polymorphisin haplotypes at the βglobin 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 βthalassemia mutations occurred on chromosomes with haplotypes 111, IX, X, and perhaps V, and a new type related to II. The mutated A_γT gene was associated with type type II, X, and the new type. Type IX was linked to a βd̀ gene and to an Xmn I site 5' to the G_γ gene, to a high G_γ globin level, and to a disease of mild severity. Type I11 was associated with a β⁺+thalassemic gene. The d̀39 mutation linked to type I1 was associated with thalassemia intermedia in three patients.