Hb Iwate was the first variant hemoglobin found in Japan (Shibata et al., 1960). Familial cyanosis had been recognized for about 200 years in the prefecture of Iwate in Honshu, where about 70 affected persons were identified in the 1950s. It was called 'kuchikuro,' or 'blackmouth.' In each form of methemoglobinemia (see 617973), the heme iron is stabilized in the ferric form. Patients with the Hb M alpha forms are cyanotic at birth; those with the Hb M beta forms are usually not cyanotic until they are 3 months of age. Horst et al. (1987) showed that the Iwate mutation involves the alpha-1 globin gene. Specifically, they demonstrated a CAC-to-TAC mutation in codon 87 of that gene. They showed that the Iwate mutation can be identified directly on RsaI digestion. See Meyering et al. (1960), Shibata et al. (1961), Gerald and Efron (1961), Miyaji et al. (1962), Heller (1962), Heller et al. (1962), Tonz et al. (1962), Shibata (1964), Tamura (1964), Shimizu et al. (1965), Pik and Tonz (1966), Maggio et al. (1981), and Mayne et al. (1986).
Ameri et al. (1999) likewise determined that the molecular defect in 2 patients with Hb M (Kankakee) was his87 to tyr in the HBA1 gene. The proportion of Hb M (Kankakee) observed was higher than that predicted for an alpha-1-globin variant. They presented evidence suggesting that the greater-than-expected proportion of Hb M (Kankakee) results from preferential association of the electronegative beta-globin chains with the alpha-(M)-globin chains that are more electropositive than normal alpha-globin chains.
