Gamma‐chain heterogeneity of fetal hemoglobin in nonblack β‐ and δβ‐thalassemia and hpfh heterozygotes and homozygotes

Abstract

The fetal hemoblobin (Hb F) of a few hundred nonblack patients with a heterozygosity or homozygosity for 0-thalassemia (0-thal), 60-thalassemia (dp-thal), and some forms of the hereditary persistence of Hb F (HPFH) was isolated by DEAE-cellulose chromatography and further characterized by high-pressure liquid chromatography. Quantitative data for the three types of y chain (A?'. A y l , and "7) were compared with those obtained for the H b F from black patients with similar conditions. The G ? chain levels in nonblack 0-thal heterozygotes varied greatly and did not fall into two distinct groups with high or low levels, a5 has been observed in blacks. The level of the Ayrchain in A y r heterozygotes did not differ significantly when this anomaly was in cis or in trans to the B-thal determinant. Beta-thalassemia homozygotes from Turkey and Yugoslavia, had "y values varying between 40% and BOc'io. Only 13 of 34 patients carried the A y r gene. Nine were A y T heterozygotes with an AyT/total *y level averaging 39% and four were A y T homozygotes.The "y chain levels in nonblack GB-thal heterozygotes varied between 28% and 46%.An additional A y T chain heterozygosity in cis to the 60-thal determinant demonstrated that over 90% of t h e r chains is produced by genes in cis to this anomaly. Analyses of members of two relatively large families with B-thal, dfi-thal, and the A y T chain heterozygosities and homozygosities occurring in different combinations allowed a more or less quantitative evaluation of the production of y-chain genes in cis or in trans to either of the two types of thalassemia determinants. Such calculations were possible both in simple heterozygotes and in persons with the P-d/3-thalassemia condition. Efremov et a1The Indian type of GyAy-HPFH heterozygosity was studied in four individuals of whom two were A y r heterozygotes. This condition differs from the black types in higher levels of G y chain and in a considerable contribution of y-chain genes in trans to the H P F H determinant. The Swiss type of HPFH heterozygosity was studied in 30 subjects belonging to six Yugoslavian families; some were A y r heterozygotes. The level of "y chain averaged over 80% in nine members of one family; the anomaly in this family deserves further study.

Haplotypes and levels of fetal hemoglobin and Gγ to Aγ ratios in mediterranean patients with thalassemia minor and major

“…Studying numerous patients with sickle cell anemia, Gilman [6] and Gilman et a1 [7] observed an excellent correlation between the genotype at the Hinc 11 restriction site in the $6 gene and the relative proportion of "y chains (about 40% when both chromosomes lack the restriction site, -/-; and at least 60% when one or both chromosomes had this restriction site, -/+ or +/+). A similar observation was made by Harano et al [3] for black P-thalassemia heterozygotes, but such data are not yet available for P-thalassemia patients from the Mediterranean area, although results of a previous study [8] suggested a wide range of Gy values in the Hb F of both 6-thalassemia heterozygotes and homozygotes.…”

“…Numerous patients with Cooley's anemia also had this type of y chain in their Hb F [8]. In our present series, only six patients with thalassemia major and three with thalassemia minor had an "yT heterozygosity, while one P-thalassemia trait mother appeared to be an "yT homozygote.…”

“…The Fig. 2) and with two nonthalassemic chromosomes (subject 1-9 with a normal chromosome carrying the AyT mutant and subject [1][2][3][4][5][6][7][8]. In all instances, the level exceeded the Ayl level (the ratio was about 2: 1 in the thalassemia major patient 1-7 and about 1: 1 in his heterozygous brother).…”

Five haplotypes in Black β‐thalassaemia heterozygotes: three are associated with high and two with low Gγ values in fetal haemoglobin

“…recent study (Efremov et al, 1982) suggested that most P-thalassaemia heterozygotes from various Mediterranean countries fell in the category with low Gy values.…”

The Hb F composition in a Moroccan Family with β°‐thalassaemia and Hb O‐Arab

“…It has been suggested that the ";( percentage in adults is genetically controlled (2)(3)(4)(5)(6)(7). We report on a family in which the propositus displays heterozygous H b 0 -A r a b (fi121 Glu + lys), a v"-thalassaemia trait, a high proportion of Hb F and a high Gy percentage.…”