Observations on the high foetal haemoglobin gene and its interaction with the thalassaemia gene

Abstract

Report of a family of mixed Indian-Portuguese ancestry with hereditary persistence of fetal hemoglobin and B-chain thalassemia. The propositus, a 17-year-old boy, had a mild hemolytic anemia characterized by slight splenomegaly, microcytosis, numerous target cells, decreased osmotic fragility, a very high level of fetal hemoglobin (75%), and normal hemoglobin A2 level. Examination of 12 other members of the family showed the following: Three individuals (father, sister, and nephew) had high levels of fetal hemoglobin (25%) but without other clinical or hematological abnormalities. Two individuals (mother and sister) had the features of thalassemia trait with increased hemoglobin A2 and normal levels of fetal hemoglobin. The condition in the propositus appears to be the result of heterozygosity for a gene which is responsible for the hereditary persistence of fetal hemoglobin (high F gene) combined with heterozygosity for a B-thalassemia gene and provides further evidence for allelism of these genes. The possible genetic basis for the high F state and B-chain thalassemia is discussed.