A FAMILY WITH HEMOLYTIC-ANEMIA AND 3 BETA-GLOBINS - THE DELETION IN HEMOGLOBIN ATLANTA-COVENTRY (BETA-75-LEU-]PRO, 141-LEU DELETED) IS NOT PRESENT AT THE NUCLEOTIDE LEVEL

Analyses of haemoglobin from a family with an unstable haemoglobin haemolytic anaemia demonstrated that the affected individuals had three beta-globins, namely, normal (beta(A)), Atlanta (beta(At)) with a mutation of beta-75 Leu --> Pro, and beta-Atlanta-Coventry (beta(At-Co)) with mutation of beta-75 Leu --> Pro and beta-141 Leu deleted. These were present in the ratio 66:23:11 respectively. The structure of the beta-globin cluster, however, was found to be normal by Southern blotting: also cytogenetic analysis failed to show any abnormality. DNA sequence analyses demonstrated the presence of the beta(At) mutation in genomic DNA isolated from leucocytes but the Coventry deletion of 141 Leu in beta(At-Co) was not present in genomic DNA. PCR amplification of the beta-globin cDNA and direct sequencing of the product also failed to demonstrate the Coventry deletion. Thus, it appears that the absence of 141 Leu in the beta(At-Co)) globin is a consequence of the beta(At) mutation in these patients and that both beta(At) and beta(At-Co) are the product of a single gene. This unusual conclusion is paralleled in the bizarre case of Hb Vicksburg where the deletion of a leucine at beta-75 is not coded for in genomic DNA.