HB Sinai-Baltimore or α₂β₂18(A15)VAL→GLY, a Silent, Mildly Unstable β Chain Variant Detected by Isoelectrofocusing and High Performance Liquid Chromatography

Abstract

Isoelectrofocusing and high performance liquid chromatographic methods were used to study an abnormal hemoglobin present in a Black male infant and his mother. The variant, named Hb Sinai-Baltimore, focused slightly behind Hb A and separated incompletely from Hb A by cation exchange high performance liquid chromatography, while the separation of the β^A and β^X chains by reversed phase high performance liquid chromatography was complete. The variant was identified through an analysis of peptides in a tryptic digest of the isolated β^X chain and by sequencing of amplified DNA which included the β-globin gene. The Val→Gly replacement at position βl8 (codon 18; GTG→GGG) or at the last position of the A helix decreases the stability of the variant without affecting the hematological parameters of 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 β^X and β^A chains in the mother with the simple Hb Sinai-Baltimore heterozygosity. An uncertainty about the α-globin gene status in the child prevented a further evaluation of these differences.