The molecular basis of HPFH in a British family identified by heteroduplex formation

Summary. Single‐base substitutions in the immediate 5′‐flanking region of the fetal ^Gγ and ^Aγ globin genes have been associated with non‐deletional forms of hereditary persistence of fetal haemoglobin (HPFH). Previously, the sole promoter mutation associated with HPFH in British individuals has been the T to C substitution at position – 198 relative to the ^Aγ globin gene CAP site. We have investigated a British family with ^Gγ HPFH and found a T to C substitution at position – 175 of the ^Gγ globin gene. The mutation was first detected by examining the amplified 5’regions of both the ^Gγ and ^Aγ globin genes for heteroduplex formation after electrophoresis in a Hydrolink gel. The potential of such a system for the study of sequence variations in the γ gene promoter regions associated with elevated HbF expression has been evaluated. Previously reported cases of an identical mutation in an American‐Black and a Sardinian family display haematological phenotypes remarkably similar to that of the British family described here.