HB TORANOMON [BETA-112(G14)CYS-]TRP] - A NEW UNSTABLE ELECTROPHORETICALLY SILENT HEMOGLOBIN

We describe a silent and unstable hemoglobin variant, Hb Toranomon, wh ich was discovered by high performance liquid chromatography in an app arently healthy Japanese male during a Hb A(1c) assay. Isoelectrofocus ing of his hemolysate and chromatographic separation of globin on a CM -cellulose column revealed no abnormality. The isopropanol precipitati on test gave a positive result. Amino acid analysis of all peptides is olated from the tryptic digests of the aminoethylated and non-aminoeth ylated beta chain (beta(A)+beta(X)) by reversed phase high performance liquid chromatography indicated a substitution of Cys-->Trp at positi on 112 of the beta chain, which was confirmed by protein sequencing. c DNA sequencing showed the nucleotide sequence of the beta 112 codon to be TGG instead of TGT, confirming the amino acid substitution describ ed above. The globin biosynthesis ratio (beta/alpha) was 1.00.