HB Mizuho or α2β268(E12)LEU→PRO in a Young Dutch Boy

Hb Mizuho is one of the more severely unstable hemoglobin (Hb) variants and is difficult to detect both by protein analysis and by sequencing of the amplified 3 chain. The instability is due to the introduction of a proline residue in helix E, of which five residues form part of the heme contact; a disturbance of this helix will undoubtedly destabilize the protein and decrease its ability to bind the heme group. Hb Mizuho was first detected in a Japanese girl using protein analytical methods (1), next in an Italian girl living in Chicago (2), while a third patient, from Kentucky, was identified through sequencing of amplified DNA (3). Here we summarize our experiences in identifying another carrier, a young boy from The Netherlands. Methodology used in the protein and DNA analyses has been detailed in Ref. 3.