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Hereditary persistence of fetal hemoglobin (HPFH) is a group of conditions in which fetal hemoglobin synthesis is not turned off with development but continues into older stage. The homozygous form of the disease is extremely uncommon, being characterized by changes in red blood cells similar to those found in heterozygous beta thalassemia. HPFH, in either the homozygous or heterozygous state, is associated with mild clinical or hematologic abnormalities. Mild musculoskeletal pains may occur infrequently, but HPFH patients are generally a symptomatic.

The disease results from failure in control of transcription from human G gamma and A gamma globin genes. Affected chromosomes fail to switch from gamma and beta chain synthesis. Expression of these genes appears to be affected substantially by formation of an intramolecular DNA triplex structure located about 200 bp upstream from the initiation site for transcription of genes, specifically between positions 194 and 215.

Hemoglobin genes of patients contain mutations in positions 195, 196,198 and 202. Mutations at 202 involve changes from C to G and C to T, at 198 from T to C, at 196 from C to T, and at 195 from C to G. These mutations influence the stability of the intramolecular DNA triple helix.

In general, the presence of polyurine-polypyrimidine sequences sufficiently long to form intramolecular triple helices tends to repress transcription, while short polyurine-polypyrimidine segments that are unable to induce triple helix formation have no effect on transcription. In the case of HPFH, a remarkable correspondence is noted between base changes that destabilize formation of the triple helix and presence of the genetics disease.