Glucose-6-phosphate dehydrogenase (G6PD) deficiency is probably the most common disease-producing genetic polymorphism of humans. Virtually all G6PD-deficient Africans show the G6PD A- phenotype, an electrophoretically rapid, deficient enzyme. The recently acquired ability to identify the point mutations producing the different variants has given us new insights into the population genetics of G6PD variants. Twenty-nine males with the G6PD A- phenotype were studied. They were of African, Mexican, Spanish, and US white ethnic origin. All had the A---G transition at nucleotide 376 characteristic of G6PD A. In each case, one of three additional mutations was present, at nucleotides 202, 680, or 968. That in this population second mutations producing G6PD deficiency occurred only on the genetic background of G6PD A suggests that G6PD A was at one time the most common type of G6PD in Africa. However, the nucleotide sequence of the chimpanzee (Pan troglodytes) G6PD indicates that the primordial human type of G6PD was G6PD B.

Several different deletions underlie the molecular basis of a-thalassemia. The most common a-thalassemia determinant in Spain is the rightward deletion (-a".'). To our knowledge, however, no cases of a-thalassemia due to nondeletional mutations have so far been described in this particular Mediterranean area. Here, we report the existence of nondeletional forms of a-thalassemia in ten Spanish families. The a,-globin gene was characterized in ten unrelated patients and their relatives only when the presence of deletional a-thalassemia was ruled out. The a,-globin gene analysis was performed using the polymerase chain reaction (PCR) followed by restriction enzyme analysis or by allelespecific priming. This allowed the identification of a 5-base pair (bp) deletion at the donor site of IVS I (aHPha) in 9 cases and the a, initiation codon mutation (aNcoa) in one case. Although these a2-globin gene mutations are found in other Mediterranean areas, our results demonstrate their presence in the Spanish population and suggest that the a H P h d genotype is probably the most common nondeletional form of a-thalassemia in Spain. o 1996 Wiley-Liss, Inc.

delta beta-Thalassemia and hereditary persistence of fetal hemoglobin (HPFH) are inherited disorders characterized by the persistent synthesis of fetal hemoglobin (HbF) during adult life. The Spanish type of delta beta-thalassemia is a mild thalassemic condition due to a large deletion starting at the Alu I repeat between the A gamma and delta-globin genes immediately 3′ to the RIH probe and extending 11 and 17 kb downstream of the 3′ endpoints of HPFH 1 and HPFH 2, respectively. Using probes from the Spanish (delta beta)zero- thalassemic DNA, the 3′ breakpoint region has been mapped to a point approximately 8.5 to 9.0 kb downstream from that of HPFH type 1 and, as we know the restriction sites 3′ to this breakpoint, the presence of the deletion can be identified with the polymerase chain reaction (PCR). In the present study, a PCR method using three specific oligonucleotides has been developed for the identification of the Spanish (delta beta)zero-thalassemia in 100 patients with delta beta- thalassemia (99 heterozygotes with mild anemia, decreased mean corpuscular volume, and 5% to 15% HbF, and one homozygote with 100% HbF and thalassemia intermedia phenotype). We conclude that the finding of the Spanish type of (delta beta)zero-thalassemia in all the patients studied here suggests Spain as the most probable origin of this thalassemic phenotype. Moreover, the amplification of the fragment encompassing the deletion junction and normal sequence is useful for the rapid molecular detection of Spanish (delta beta)zero-thalassemia.

Loss of the p53 gene alleles was investigated in 26 patients with Ph+, BCR/ABL+ chronic myeloid leukemia (CML) by means of the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis using the restriction enzyme AccII. In all cases, peripheral blood and/or bone marrow samples were obtained at different times during the chronic phase of the disease and at blast crisis, and in some of them also at the accelerated phase. Of the 12 cases considered informative, 11 evolved into myeloid type blast crisis and one into a lymphoid blast crisis, whereas only two showed an i(17q) chromosome at cytogenetic study. In four of the 12 informative cases, a loss of one p53 gene allele was observed, in all cases coincident with the development of the accelerated phase or blast crisis. One patient with a deleted p53 gene allele, in whom it was possible to analyze the gene structure in the three CML evolutive phases (chronic and accelerated phases and blast crisis), showed loss of the p53 gene allele in both the accelerated and the blastic phase, but not during the chronic phase. On the other hand, one of the two cases with an i(17q) chromosome exhibited one allelic deletion of the p53 gene. Thus, the relatively frequent monoallelic deletion of the p53 gene coincident with the appearance of the blast crisis registered in the present study would support a possible role of the p53 gene alterations in the evolution of CML to its final stages.