A frequent A gamma-hereditary persistence of fetal hemoglobin in northern Sardinia: its molecular basis and hematologic phenotype in heterozygotes and compound heterozygotes with beta-thalassemia.
A survey of hemoglobinopathies in northern Sardinia revealed a high frequency (0.3%) of carriers of a hematologic condition characterized by increased expression of fetal hemoglobin during adult life (hereditary persistence of fetal hemoglobin or HPFH). In spite of a normal hematologic phenotype, the heterozygous carriers for this condition display about 12% HbF, almost exclusively of the A gamma type; compound heterozygotes with beta-thalassemia have 20%-26% HbF and run a very mild clinical course. The sequence analysis of the cloned A gamma gene linked to the HPFH determinant revealed the presence of a G----A substitution at position -117 of the A gamma-globin gene promoter; the same mutation occurs also in Greek HPFH, although associated with different restriction polymorphisms. Another hereditary condition characterized by increased HbF (alpha 2 A gamma 2) level and a mild thalassemia phenotype in Sardinia is associated with the -196C----T substitution in the A gamma-globin gene promoter (Sardinian delta beta-thalassemia). Population studies using oligonucleotides complementary both to the -117 G----A and -196C----T mutations and the corresponding normal sequences confirm the presence of these mutations only in HPFH and delta beta-thalassemia chromosomes and exclude these changes being common DNA polymorphisms.
D005260:Female; D005319:Fetal Hemoglobin / Q000235:genetics*; D005914:Globins / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007558:Italy; D008297:Male; D009154:Mutation; D009693:Nucleic Acid Hybridization; D010375:Pedigree; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D013789:Thalassemia / Q000097:blood / Q000235:genetics*
D005914:Globins; D005319:Fetal Hemoglobin