Rapid detection of Spanish (δβ)°-thalassemia deletion by polymerase chain reaction

Abstract

δβ-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 δβ-thalassemia is a mild thalassemic condition due to a large deletion starting at the Alu I repeat between the Aγ and δ-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 (δβ)°-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 (δβ)°-thalassemia in 100 patients with δβ-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 (δβ)°-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 (δβ)°-thalassemia. © 1992 by The American Society of Hematology.