Homozygotes for the hereditary persistence of fetal hemoglobin: The ratio of G? to A? chains and biosynthetic studies

Abstract

Two sons of a previously reported Ghanaian homozygote for the hereditary persistence of fetal hemoglobin (HPFH) (Ringelhann et al., 1970) also are HPFH homozygotes. In addition, another unrelated adult Ghanaian homozygote has been detected. All of these Ghanaian homozygotes as well as three American Black HPFH homozygotes have the G gamma A gamma type of HPFH with a G gamma to A gamma ratio of about 3:2, in contrast to an Asiatic Indian homozygote who has the G gamma type. Globin chain synthesis in HPFH homozygotes is unbalanced, with a gamma/alpha ratio of 0.6 or less, whereas it is balanced in heterozygotes according to most reports.

Analysis of the <i>γ</i> Chains in a Homozygote for HPFH Negro Type and in Three Related Heterozygotes

“…The Gy/Ay ratio observed in the homozygote in our laboratory is about 7/3 and is in keeping with the data obtained in the same subject by Ringelhann et al [15]; it must be underlined that all the hom ozygotes up to now studied present a Gy/Ay ratio of fetal type [15], always higher than that reported in the heterozygotes. In partic ular, in family M., described by Huisman et a!.…”

“…Up to now several subjects, both heter ozygous and homozygous for HPFH Negro type, have been studied with regard to the y chain composition [7,15]; however, only in a few cases complete family studies were carried out in order to evaluate the inherit ance of the y gene expression [7],…”

“…The proposi tus was firstly examined by Acquaye et al 12] and his glycine/alanine ratio at position 136 was already studied by Ringelhann et al [15]. The y 136 glycine/alanine ratio was deter mined after cleavage of 10 mg whole globin F with 100-fold molar excess of CNBr in 70% for mic acid at room temperature for 24 h. CNBr was eliminated by vacuum drying and the residue was fingerprinted on paper at pH 6.4 in order to sepa rate the r-CB3 fragment as described by Bernini et al …”

Genome editing using CRISPR-Cas9 to create the HPFH genotype in HSPCs: An approach for treating sickle cell disease and β-thalassemia

“…This study provides proof of concept for developing a potential new approach to autologous transplantation therapy for the treatment of homozygous β-thalassemia and SCD. molecular level (12,13,(19)(20)(21)(22)(23)(24) (Fig. S1A).…”

“…Some of the deletion group that exhibit pancellular distribution of hemoglobin seem to have no serious ill effect (11). Several individuals homozygous for deletional HPFH express only HbF and are healthy (12,13). Individuals doubly heterozygous for this type of HPFH and β-thalassemia or SCD have minimal or mild clinical consequences in contrast to the serious illness in patients homozygous for these diseases (14,15).…”