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

Br J Haematol. 1994 Aug;87(4):797-804. doi: 10.1111/j.1365-2141.1994.tb06740.x.

Abstract

The beta-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 G gamma- and A gamma-globin genes. Two individuals suspected of having a beta-thalassaemia gene linked to the high HbF condition also had a normal beta-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 A gamma-globin allele was detected in one subject and was confirmed by dot-blot hybridization. Restriction fragment length polymorphisms in the beta-globin gene cluster showed that the 5' haplotype (-+-++) and the presence (+) of an Xmm 1 polymorphic site at -158 of the G gamma-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Base Sequence
  • Female
  • Fetal Hemoglobin / analysis
  • Fetal Hemoglobin / genetics*
  • Globins / genetics*
  • Haplotypes
  • Hemoglobinopathies / genetics*
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • Thailand
  • Thalassemia / genetics*

Substances

  • Globins
  • Fetal Hemoglobin