Hereditary persistence of foetal haemoglobin: A family study suggesting allelism of the F gene to the S and C haemoglobin genes

ABSTRACT

A large family is described in which the inheritance of a gene responsible for high levels of foetal haemoglobin (the F gene) and its interaction with the gene for haemoglobin-S is followed through three generations. Four cases of SF combination are reported. An example of the the CF combination is described. Evidence is produced that the F gene is situated at the same locus as the S and C genes and the gene for classical thalassaemia, and that it is therefore an allele of them. As an altenative explanation it is suggested that the high levels of foetal haemoglobin may not result from direct gene action but may be due to a failure of inheritance of normal haemoglobin following a deletion at the A-S-C locus (or a mutation lethal for beta-chain production), with a consequent revival of the dormant mechanism of foetal haemoglobin synthesis. Sickle-cell anaemia and the SF combination are phenotypically indistinguishable, and the difficulties in explaining the very marked clinical difference between them are discussed (Summary)