Double Heterozygosity for Two Unstable Haemoglobins: Hb Sydney (β67[E11] Val→Ala) and Hb Coventry (β141[H19] Leu Deleted)

Abstract

A 7‐year‐old English girl was found to have a lobar pneumonia with a marked haemolytic anaemia. Routine electrophoresis revealed no abnormal haemoglobin but, as anticipated, an unstable haemoglobin fraction readily formed in haemolysates on routine in vitro instability tests. From the subsequent structural and biosynthetic studies it was concluded that the propositus' red cells contained, in addition to Hbs A, A 2 and F, two unstable haemoglobins with abnormalities in the primary structure of their non α‐chains: Hb Sydney and Hb Coventry. The first has an amino acid substitution Val→Ala at position β67 (E11), while the other, Hb Coventry, is a new variant with a non α‐chain which resembles the β A ‐chain except that the leucine residue at position β141(H19) is deleted. This suggests that, instead of the normal complement of two β‐chain genes, the propositus' genome has three, i.e. β A ‐, β Sydney ‐ and β Coventry ‐chain genes. Evidence is presented from which it can be concluded that the non α‐chain of Hb Coventry, whilst being structurally a β‐chain variant is, in fact, a βδ fusion chain variant with 140β‐ and 5δ‐chain residues. The oxygen dissociation curve of the propositus showed a reduced affinity at the upper part of the curve, a feature which she shared with a straightforward heterozygote for Hb Sydney, and a slight shift to the left in the lower part, a feature which she shared with her father who possessed Hb Coventry.