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

Abstract

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