HB UTRECHT [ALPHA(2)129(H12)LEU-]PRO], A NEW UNSTABLE ALPHA-2-CHAIN VARIANT ASSOCIATED WITH A MILD ALPHA-THALASSEMIC PHENOTYPE

We describe a new alpha(2)-globin gene point mutation found in six ind ividuals of a three-generation Dutch family. The mutant, which is asso ciated with a mild alpha-thalassaemic phenotype, is not detectable at the protein level, The alpha(2) cd129 (CTG-->CCG) transition was found by molecular analysis using denaturing gradient gel electrophoresis ( DGGE) and single-strand conformation analysis (SSCA) followed by direc t sequencing of the alpha(2)-globin gene. Southern analysis revealed a triplication of the zeta-gene in cis with the mutant alpha-globin gen e.