HB SINAI-BALTIMORE OR ALPHA(2)BETA(2)18(A15)VAL-]GLY, A SILENT, MILDLY UNSTABLE BETA-CHAIN VARIANT DETECTED BY ISOELECTROFOCUSING AND HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY

Isoelectrofocusing and high performance liquid chromatographic methods were used to study an abnormal hemoglobin present in a Black male inf ant and his mother. The variant, named Hb Sinai-Baltimore, focused sli ghtly behind Hb A and separated incompletely from Hb A by cation excha nge high performance liquid chromatography, while the separation of th e beta(A) and beta(X) chains by reversed phase high performance liquid chromatography was complete. The variant was identified through an an alysis of peptides in a tryptic digest of the isolated beta(X) chain a nd by sequencing of amplified DNA which included the beta-globin gene. The Val->Gly replacement at position beta18 (codon 18; GTG underbar-> GGG underbar) or at the last position of the A helix decreases the sta bility of the variant without affecting the hematological parameters o f its carrier. The propositus was a compound heterozygote for Hb Sinai -Baltimore and Hb S; the relative quantities of the two variant chains were somewhat different from those of the beta(X) and beta(A) chains in the mother with the simple Hb Sinai-Baltimore heterozygosity. An un certainty about the alpha-globin gene status in the child prevented a further evaluation of these differences.