Genomic approaches to identifying targets for treating β hemoglobinopathies.

Sickle cell disease and β thalassemia are common severe diseases with little effective pathophysiologically-based treatment. Their phenotypic heterogeneity prompted genomic approaches to identify modifiers that ultimately might be exploited therapeutically. Fetal hemoglobin (HbF) is the major modulator of the phenotype of the β hemoglobinopathies.

Fetal haemoglobin levels and haematological characteristics of compound heterozygotes for haemoglobin S and deletional hereditary persistence of fetal haemoglobin.

Compound heterozygotes for sickle haemoglobin (HbS) and hereditary persistence of fetal haemoglobin (HPFH) have high fetal haemoglobin (HbF) levels but few, if any, sickle cell disease-related complications. We studied 30 cases of HbS-HPFH (types 1 and 2), confirmed by molecular analysis, and report the haematological features and change in HbF levels over time. These results were compared to those of patients with sickle cell anaemia or HbS-β(0) thalassaemia, including a subgroup of patients carrying the XmnI polymorphism, known to be associated with elevated HbF.