Hb Takamatsu (β120〔GH3〕Lys→Gln) : Study of Ten Families including a Homozygote, and Application of New Methods of Peptide Mapping

Eighteen heterozygous carriers of abnormal hemoglobin were discovered in a survey of 23,000 individuals in Takamatsu area by means of isoelectric focusing. Accordingly, the incidence of abnormal hemoglobin in this area is 1/1,280 or 0.08% with a 90% confidence interval of 1/900-1/2,100. This figure is approximately 2.7 times that in other parts of Japan (1/3, 620 or 0.03%). In eleven of the eighteen, the abnormal hemoglobin was identified as Hb Takamatsu. Five different abnormal hemoglobins were identified in the remaining seven and were reported elsewhere. Structural analysis of Hb Takamatsu by the traditional methods demonstrated a new amino acid substitution, β12OLys→Gln, in the initial three examples. These procedures demanded, however, a relatively large amount of sample because the filter-paper fingerprinting did not separate the abnormal βT12b・13 from βT8・9. The author invented two new techniques of peptide mapping. One was phosphocellulose column chromatography, which proved quite efficient in the purification of the abnormal β T12b-13. The other was silica gel thin-layer fingerprinting, which was superior to the conventional filter-paper method with better resolution of all tryptic peptides. The new techniques enabled rapid identification of Hb Takamatsu from only 2 ml of blood in the eight subsequent examples. A homozygote of Hb Takamatsu, the first instance of homozygosity for an abnormal hemoglobin in Japan, was discovered by family study. The homozygote was a twelve-year-old girl who appeared to have been quite healthy, and no abnormality was found in routine physical and laboratory examinations. This was to be expected from the normal oxygen affinity and stability of Hb Takamatsu. It is conjectured that Hb Takamatsu gene had occurred in a distant past, and was not subjected to natural selection, and has accumulated in the small, rather isolated area.