T. Nakatsuji

(Aγδβ)°-Thalassaemia in Blacks is due to a deletion of 34 kbp of DNA

DNA from members of 10 Black families with conditions considered to be Gγδβ)°‐thalassaemia or Gγδβ)°‐HPFH were studied by using restriction enzyme analysis. One or more affected members from each family were shown to have the same deletion of 34 kbp of DNA in the human β‐globin gene cluster. A clone spanning the deletion was isolated from the DNA of one such person and studied in detail. The deletion removed part of the Aγ and all of the Ψβ, δ and β‐globin genes and is different from the four previously identified deletions which caused a condition presently known as (Aγδβ)°‐thalassaemia.

Restriction endonuclease gene mapping studies of an Indian (Aγδβ)°-thalassaemia, previously identified as Gγ-HPFH

Summary. Restriction endonuclease mapping data are presented for the DNA of a young Indian homozygous patient (and his heterozygous parents) who were identified 10 years ago as having a Gγ‐hereditary persistence of fetal haemoglobin (Sukumaran et al, 1972). However, the present results indicate a genetic lesion in these persons which is similar to that observed in another Indian with (Aγδβ)°‐thalassaemia homozygosity (Amin et al, 1979) and is characterized by two relatively short deletions and an inversion involving the Aγ,δ and β globin genes (Jones et al, 1981a). Some additional blot hybridization studies have provided further data confirming the deletion‐inversion hypothesis.

Hb F-Columbus-Ga or a2 Gγ2 94(FGJ)Asp→Asn

A new γ chain variant with an electrophoretic mobility at pH 8.1 between those of Hb S and Hb C was isolated and quantitated by DEAE-cellulose chromatography. It was readily identified with the use of various micro-chromatographic and sequencing procedures as α2Gγ2 94(FGl)Asp→Asn. The hemoglobin was named Hb F-Columbus-Ga. The quantity of this GY chain variant (as % total γ chain) was about 39% and the percentages of the normal Gγ and AγI chains were 37% and 24%, respectively.

Hb F-Kennestone or α2Gγ2 (EF1)77 His → Arg Observed in a Caucasian Baby

During our continuing attempts to characterize fetal hemoglobins (Hb F) with abnormal γ chains and abnormality was observed in a Caucasian female newborn which upon further analysis was found to be a His→Arg substitution at position 77 of the Cγ chain.

Hb Cordele alpha(2)47 (CE5)Asp----Ala beta 2. A mildly unstable variant observed in black twins.

Hb Cordele, which has an Asp----Ala substitution at position 47 (CE5) of the alpha chain, was discovered in Black twins living in Cordele, Georgia. The structure of this variant was elucidated through analyses of tryptic peptides of the alpha chain which were isolated by high performance liquid chromatography. At birth, Hb Cordele accounted for about 21-23% of total hemoglobin, and for 30.4% in one of the babies at age 3.5 months. Hb Cordele has a normal oxygen affinity, but is mildly unstable at 60 degrees C. Some of its properties have been compared with those of Hb Kokura (alpha 47 Asp----Gly), Hb Hasharon (alpha 47 Asp----His), and Hb Arya (alpha 47 Asp----Asn). Studies on an adult carrier of Hb Cordele were not possible.

Hb Etobicoke, α85(F5) Ser → Arg Found in a Newborn of French-Indian-English Descent

During a recent testing program for hemoglobin (Hb) abnormalities in cord bloods of newborns in the State of Georgian an α-chain variant was discovered in a male Caucasian infant of French-Cherokee Indian-English descent. The hematological values of the infant at five weeks were: Hb 8.9 g/dl, RBC 2.99 × 1012/1; PCV 0.28 1/1, MCV 93 fl, MCH 30.4 pg, and MCHC 31.2%. Corresponding results on both parents were normal. Although the abnormal Hb was not found in either parent, paternity studies were not done. The variant had a mobility of Hb G on cellulose acetate electrophoresis at PH 8.6 and could not be detected by citrate agar electrophoresis at pH 6.1 (1). DEAE-cellulose chromatography with glycine-KCN-NaCl developers (2) redily separated the abnormal Hbs from Hb A, Hb F, and Hb F1 partially separated Hb Fx from Hb X. The combined concentration of the Hb Fx was 16% in the cord blood red cell lysate. A repeat chromatogram at five weeks of age showed improved separation and gave the concentration of Hb Fx as ...

Hb F-Bonaire-Ga or αAγ239(C5) Gln→Arg, Characterized by High Pressure Liquid Chromatographic and Microsequencing Procedures

A slowly moving γ chain variant was discovered in the cord blood of a baby of English-Vietnamese descent. The abnormality concerned the substitution of Gin residue in position 39(C5) of the Aγ chain by an Arg residue resulting in an -Arg-Arg-sequence at positions 39 and 40. The quantity of the Ay chain variant was nearly 10% of the total Hb F with 15% of the Hb F having normal Aγ chains and 75% of Hb F having Gγ chains. High pressure liquid chromatographic and microsequencing methods greatly facilitated the structural analyses.

A New γ Chain Variant: Hb F-Pordenone [γ6(A3) GLU à GLN: 75ILE: 136ALA]

In a survey of Italian newborn babies, one baby boy was found to have a new fetal hemoglobin variant which is characterized by a GluaGln substitution at position γ6(A3). This variant had an isoleucine at position γ75 and an alanine at position γ136.