Severe Hb S-β°-thalassaemia with a T→C substitution in the donor splice site of the first intron of the β-globin gene

Through direct sequencing and dot-blot analyses with synthetic oligonucleotide probes of amplified DNA, a new nucleotide substitution was discovered in a Black teenager with severe Hb S-β°-thalassaemia. The substitution involved a T→C replacement at the second position of the donor splice site of the first intervening sequence of the β-globin gene. The clinical and haematological observations made in Black subjects with Hb S-β°-thalassaemia, with different types of thalassaemia, suggest severe disease resembling sickle cell anaemia. Only an occasional patient had a milder clinical course, perhaps because of a greatly increased production of fetal haemoglobin.