MOLECULAR CHARACTERIZATION OF VIETNAMESE HPFH

A novel 30 kb deletion of the beta-globin gene cluster associated with the phenotype of hereditary persistence of fetal hemoglobin (HPFH) is described in two unrelated individuals of Vietnamese background. The Vietnamese GgammaAgamma HPFH deletion has a unique 5' breakpoint 3.5 k b downstream of the delta-globin gene. The 3' breakpoint lies approxim ately 8 kb upstream from the HPFH-3 breakpoint (Henthorn et al., 1986) and in the region of the 3' breakpoints of HPFH-4 (Saglio et al., 198 6), German and Belgian Ggamma+ (Agammadeltabeta)-degrees-thalassemias (Anagnou et al., 1988; Losekoot et al., 1991). Characterisation of the 3' breakpoint in the present study has enabled more precise localisat ion of other deletion breakpoints at this locus. Further evidence is p rovided that the 3' breakpoint region contains functionally important sequences and that the juxtaposition of these sequences to the gamma-g lobin genes is a significant factor in the increased fetal hemoglobin levels. (C) 1993 Wiley-Liss, Inc.