A molecular study of a family with Greek hereditary persistence of fetal hemoglobin and beta-thalassemia.

摘要: A family was studied in which two inherited defects of the non-alpha-globin cluster segregate: Greek hereditary persistence fetal hemoglobin (HPFH) and beta-thalassemia. Fragments from patients were cloned cosmid phage lambda vectors, assigned to either HPFH or beta-thalassemic chromosome on basis demonstration a polymorphic BglII site gamma-globin cluster. The thalassemic beta-globin gene carries mutation at nucleotide 1 intervening sequence I, known cause beta zero-thalassemia; is entirely normal, both intron-exon 5' flanking regions required for transcription. As compound HPFH/beta-thalassemia heterozygote synthesizes HbA, these data prove that functional, although decreased rate; its lower activity likely be due distant mutation. shows only mutations: T----C substitution large (responsible site) C----T 196 nucleotides cap site; normal up -1350 upstream gene. Circumstantial evidence suggests -196 may responsible abnormally high expression