HB Handa [alpha 90 (FG 2) Lys replaced by Met]: structure and biosynthesis of a new slightly higher oxygen affinity variant.
Hb Handa, an abnormal hemoglobin which isoelectrofocused anodally to Hb A, was found in a 15-year-old Japanese girl and her mother, who were apparently healthy. Clinical and hematological examinations showed no abnormality in individual heterozygous for this mutant gene except for a slight increase of reticulocyte count (2.1-2.4%). Structural studies disclosed an alpha chain anomaly and substitution of alpha 90 (FG 2) Lys replaced by Met. The content of the abnormal hemoglobin in the hemolysate was 17.5-18.3% of the hemoglobin. The isopropanol precipitation test was negative. The purified abnormal hemoglobin showed a slightly higher oxygen affinity than that of Hb A, but Hill's n constant, Bohr effect and organic phosphate effect were within the normal range. Globin chain biosynthesis in reticulocytes indicated that the production rate of the abnormal alpha chain was suppressed to 38% of the normal level.