Heterocellular hereditary persistence of fetal hemoglobin (HPFH). Molecular mechanisms of abnormal gamma-gene expression in association with beta thalassemia and linkage relationship with the beta-globin gene cluster

• Published in: Human genetics Vol. 66; no. 2-3; p. 151
• Main Authors: Giampaolo, A, Mavilio, F, Sposi, N M, Carè, A, Massa, A, Cianetti, L, Petrini, M, Russo, R, Cappellini, M D, Marinucci, M
• Format: Journal Article
• Language: English
• Published: Germany 01.01.1984
• Subjects: Adolescent; Adult; Aged; Child; Chromatography, High Pressure Liquid; Chromosome Mapping; DNA Restriction Enzymes; Female; Fetal Hemoglobin - analysis; Fetal Hemoglobin - genetics; Genetic Linkage; Globins - genetics; Hemoglobin A - analysis; Hemoglobin A - genetics; Hemoglobin A2 - analysis; Hemoglobin A2 - genetics; Heterozygote; Humans; Italy; Male; Middle Aged; Pedigree; Thalassemia - blood; Thalassemia - genetics; Italy
• ISSN: 0340-6717
• DOI: 10.1007/BF00286590

We report a study of four families of Italian origin in which heterocellular HPFH is inherited linked to beta thalassemia over two or three generations. The HPFH + beta thalassemia carriers showed thalassemic blood pictures and elevated HbF and F-cell number without increase in the HbF/F-cell content. Association of this gene complex with a second beta thalassemia trait gives rise to a mild clinical picture characterized by 9-12 g/dl of mainly HbF in peripheral blood and no transfusion requirement. In two families, independent segregation of the HPFH or beta-thal trait was observed, and in one case the study of the DNA polymorphisms within the gamma delta beta gene cluster indicated that the HPFH mutation lies outside that DNA region. In one family the coexistence of a polymorphic variant of the A gamma chain (the A gamma T chain) allowed us to demonstrate that the increased gamma chain synthesis caused by the heterocellular HPFH determinant is directed by both chromosomes.