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The cord blood sample of a Caucasian newborn contained about 40% of an abnormal fetal hemoglobin. The mutated gamma chain was isolated using reversed phase high performance liquid chromatography and characterized by means of electrospray and fast atom bombardment mass spectrometric techniques as a G gamma-globin variant with an Ile-->Thr substitution at position gamma 75. The variant chain shows the same structure as the previously described Hb F-Charlotte that was demonstrated to be an A gamma variant with an Ile-->Thr substitution at position gamma 75 and an additional Ala-->Gly substitution at gamma 136.

In each of two families from Sardinia, Italy, we have found segregation for two alpha-chain hemoglobin variants, which we have identified as G Philadelphia [alpha 68 (E17) Asn leads to Lys] and J Sardinia [alpha 50 (CE8) His leads to Asp], respectively. One family also shows segregation for the beta-thalassemia trait. One subject in one family and two subjects in the other family have in their red cells both hemoglobin variants, G and J, in addition to HbA. One of the subjects, a newborn baby, has six major hemoglobin components; alpha 2A beta 2, alpha 2A gamma 2, alpha 2G beta 2, alpha 2G gamma 2, alpha 2J beta 2, alpha 2J gamma 2. These three cases are to be added to three previous cases in the literature in whom three different alpha-chains have been found in the same blood. These findings prove that the alpha-chain locus is duplicated in the Sardinian population, as it is in other populations. The relative amounts of the various hemoglobin species found in members of our two families, through three and four generations respectively, suggest that chromosomes with and without duplication may coexist in the same population.

The hemoglobin of 2048 newborn babies from Sardinia was analyzed by isoelectric focusing and polyacrylamide gel electrophoresis in order to determine the level of Hb F-Sardinia (with A gamma T) and the G gamma chain. Hb F-Sardinia values of 15.5 +/- 2.6% were present in the A gamma T heterozygote whereas 30.7 +/- 5.2% were present in the homozygote. The A gamma T gene frequency was 0.17. Most of the babies tested showed the normal G gamma level either in the absence of the A gamma T anomaly (69.6 +/- 4.1%), or in the presence of the anomaly in both the heterozygous state (70.9 +/- 4.8%) and the homozygous state (71.1 +/- 3.4%). Similar values were shown in nine homozygotes for beta-thalassemia discovered during the screening. Nine newborn babies (0.44%) showed particularly low G gamma levels (38.3 +/- 6.8%) whereas 18 newborn babies showed high G gamma levels (83.9 +/- 2.6%). The frequencies of the anomalies (0.0022 for the low G gamma and 0.0044 for the high G gamma) were the lowest observed in Caucasian and other ethnic groups. Data suggest the presence of abnormal gamma globin gene arrangements in the Sardinian population.