Nondeletional type of hereditary persistence of fetal haemoglobin: molecular characterization of three unrelated Thai HPFH

Summary The β-globin gene clusters of three unrelated Thai families with a nondeletional type of hereditary persistence of fetal haemoglobin (HPFH) were studied using polymerase chain reaction-related techniques. All appeared to have normal nucleotide sequences from the Cap site to position -400 of both the Gγ- and Aγ-globin genes. Two individuals suspected of having a β-thalassaemia gene linked to the high HbF condition also had a normal β-globin gene sequence, spanning from position -108 from the Cap site to the polyadenylation site. Deletion of four nucleotides, AGCA, at positions -225 to -222 of one Aγ-globin allele was detected in one subject and was confirmed by dot-blot hybridization. Restriction fragment length polymorphisms in the β-globin gene cluster showed that the 5’ haplotype (- + - ++) and the presence (+) of an Xmn 1 polymorphic site at -158 of the Gγ-globin gene are associated with the high F phenotype in these families. Direct sequencing of the 5’ hypersensitive-2 (5’ HS-2) site of the locus control region (LCR) showed that this Xmn, 1 (+) site is also linked to a specific rearrangement of TA repeats (TA)9CACATATACG(TA)10, in HS-2 segment.