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

• Published in: Hemoglobin Vol. 17; no. 6; p. 505
• Main Authors: Pobedimskaya, D D, Molchanova, T P, Amernick, R, Druskin, M S, Webber, B B, Wilson, J B, Huisman, T H
• Format: Journal Article
• Language: English
• Published: England 01.12.1993
• Subjects: Chromatography, High Pressure Liquid; Female; Hemoglobins, Abnormal - analysis; Hemoglobins, Abnormal - genetics; Heterozygote; Humans; Infant; Isoelectric Focusing; Male; Mutation
• ISSN: 0363-0269; 1532-432X

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 beta A and beta 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 beta X chain and by sequencing of amplified DNA which included the beta-globin gene. The Val->Gly replacement at position beta 18 (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 beta X and beta A chains in the mother with the simple Hb Sinai-Baltimore heterozygosity. An uncertainty about the alpha-globin gene status in the child prevented a further evaluation of these differences.