A 59-year-old man with β -thalassaemia major is unusually well. He has no γ -chains in his haemoglobin but is heterozygous for the genes responsible for α^A and for α^G Philadelphia. In addition he is also heterozygous for the genes responsible for γ^F and a new γ-chain, γ⁷⁵ (E¹⁹) Ile – Thr, named γ^F.Sardinia. It was not possible to isolate the mutant γ-chain, but from the overall ratios of Gγ-:Aγ-Chain and γ⁷⁵Ile : γ⁷⁵ Thr_; it could be inferred that the mutation had presumably occured in the Gγ-chain. Some of the propositus’ siblings have high levels of Hb A₂, and it is suggested that they possibly carry a gene for a Lepore chain with the δβ -crossover after residue δ126.

No abstract

Fetal haemoglobin consists of α- and γ-chains. There are two types of human γ-chains:one, (Gγ) in which residue 136 is one of glycine, and another (Aγ), in which that position is occupied by a residue of alanine. Some time ago a homozygote for the high persistent fetal haemoglobin gene was found in Ghana whose sole red cell pigment was fetal haemoglobin. The nature of the fetal haemoglobin in this individual has now been determined. It is entirely of the Gγ-type.

In a newborn twin with haemolytic anaemia an unstable fetal haemoglobin was found to be the cause. The anaemia improved spontaneously with the disappearance of the fetal haemoglobin. The new Hb F (alpha2gamma2) variant was shown to have a glycine at position 130 of the 146 residues of the gamma chain. This portion is inside the globin molecule and in all known normal globins it is occupied by a residue with a bulky hydrophobic side chain. Its replacement by glycine which has no side chain would be expected to cause instability. The human gamma-chains may either have a glycine or an alanine at position 136. Evidence is brought forward to suggest that in the abnormal chain position 136 is occupied by glycine.

An abnormal haemoglobin, which on paper electrophoresis has the mobility of Hb J, has been found in two brothers and, in the heterozygousstate at least, is not associated with serious clinical abnormality. The structure of this hitherto unreported haemoglobin is a 120(H3) Ala -+ Glu and it is named Haemoglobin J Birmingham.A fast moving haemoglobin whose electrophoretic mobility on paper at pH 8.6 was similar to that of HbJ, was discovered in two brothers from Bangladesh during a pilot study of abnormal haemoglobins in immigrant Birmingham schoolchildren. This component appeared to represent approximately 20% of the total haemoglobin. MATERIAL AND METHODSThe initial screening for abnormal haemoglobins was performed on capillary blood samples as previously described by Stuart, Schwartz, Little and Raine (1973). On detection of the abnormal haemoglobin, the boys were asked to attend Birmingham Children's Hospital for clinical examination and further haematological investigations, which followed standard methods (Dacie and Lewis, 1968).Blood was haemolysed as previously described (Lehmann and Huntsman, 1974). Electrophoresis of the haemolysate was done on paper in Tris-buffer, pH 8.9 (Cradock-Watson et aI., 1959) and on starch gel, pH 8.3 (Smithies, 1959).For structural studies, the haemolysate was chrornatographed on a DEAE Sephadex A-50 column (Huisman and Dozy, 1965) at 4°C, using a linear gradient pH 8.2-7.2 (Tris-HCI buffer) to isolate the HbJ. All fractions were concentrated by ultrafiltration using a Sartorius Collodion bag.Haem was removed by 1.5 % HCI-acetone precipitation at -20°C (Rossi-Fanneli et al., 1958) and the precipitated globin washed four times with acetone at -20°C, to remove HCI, then dried under nitrogen. The abnormal ex chain was isolated using a minor modification of the procedure of Clegg, Naughton and Weatherall (1966) and then dialysed against 0.5 % formic acid and Iyophilised.By methods described previously (Lehmann and Huntsman, 1974;Sick et al., 1967), the abnormal o-chain was digested with trypsin (TPCK treated, Worthington Biochemicals Corp., N.J.) and twodimensional paper chromatograms (fingerprints) prepared for diagnostic and preparative purposes. The insoluble tryptic peptides were digested with pepsin and fingerprints prepared (Lorkin et al., 1970.) Peptides on fingerprints were identified by staining either with ninhydrin, 0.2 g/IOO ml (for diagnostic fingerprints), or ninhydrin, 0.02 g/IOO ml (for preparative fingerprints). The diagnostic fingerprints were further stained for sulphur