Two new alpha-thalassemia point mutations that are undetectable by biochemical techniques.

We report two new point mutations causing alpha-thalassemia (alpha-thal) that could not be characterized by conventional biochemical studies. The first mutation is a single base substitution at codon 123 of the alpha1-globin gene [alpha123(H6)Ala-->Pro, GCC>CCC (alpha1)] and leads to the substitution of a proline residue in the H helix. The resulting unstable hemoglobin (Hb) variant has been named Hb Voreppe. The second is a frameshift of the alpha2 gene due to a deletion (-C), either of the third base of codon 112 or of the first base of codon 113, that causes a premature stop codon at position 132.