HB SHELBY BETA-131(H9)GLN-!LYS! IN ASSOCIATION WITH HB-S BETA-6(A3)GLU-!VAL! - CHARACTERIZATION, STABILITY, AND EFFECTS ON HB S POLYMERIZATION

When first tested for abnormal hemoglobins, a 2-year-old boy, appeared to have Hb F, Hb S and Hb A2. Confirmatory testing revealed a beta ch ain variant inherited from his father and beta(S) from his mother. Ana lysis of tryptic peptides in conjunction with automated DNA sequence a nalysis showed that the variant hemoglobin was Hb Shelby beta131 (H9) Gln --> Lys (CAG underbar --> AAG underbar)!. Heat and mechanical stab ilities of various liganded Hb Shelby tetramers were compared to those of Hb A and Hb S. Oxy-Hb Shelby precipitated more readily than oxy-Hb A, but was much more stable than oxy-Hb S during mechanical agitation . In contrast, oxy-Hb Shelby was much less stable than oxy-Hb A and ox y-Hb S following heat treatment. Met-Hb Shelby was most unstable compa red to other liganded forms of Hb Shelby, while deoxy- and carbonmonox y-forms of Hb Shelby showed similar heat-induced precipitation rates. These data indicate that heat instability of Hb Shelby is accompanied by heme oxidation, and that denaturation by mechanical agitation occur s in the absence of heme oxidation. Hb Shelby, like Hb A, can form hyb rids with Hb S which participate in polymer formation in vitro. Howeve r, Hb S/Hb Shelby hybrids copolymerized with Hb S less than A/S hybrid s. Since the patient's MCHC value is normal, this finding Coupled with the elevated Hb A2 and Hb F levels, both of which are known to inhibi t polymerization of Hb S, may contribute to the patient's mild clinica l presentation.