Hemoglobin Indianapolis (beta 112[G14] arginine). An unstable beta-chain variant producing the phenotype of severe beta-thalassemia.

Abstract

A B S T R A C T Hemoglobin (Hb

Molecular analysis of the beta-thalassemia phenotype associated with inheritance of hemoglobin E (alpha 2 beta2(26)Glu leads to Lys).

“…The Hb Lepore and Hb Constant Spring hemoglobins (2,3,35) are the best known examples. More recently, Hb Indianapolis, a /-chain mutant, has been shown to produce /8-thalassemia by profound posttranslational instability of the newly assembled ,8-variant, preventing combination with a-globin to form hemoglobin tetramers (18). Finally, we have described a profound reduction in the mRNA coding for the ,8-chain of Hb Vicksburg (/375 beu0 ), which exhibits a /8-thalassemia phenotype (39).…”

“…The hemolysates were then extracted with phenol for preparation of reticulocyte RNA, using methods previously described (17). (18); the suspension was preincubated for 5 min at 370C with gentle shaking prior to the addition of isotope. For short-term, pulse-chase labeling studies, 200 ACi of [3H]leucine was added to 3 cm3 of prewarmed cell suspension.…”

Molecular basis for nondeletion alpha-thalassemia in American blacks. Alpha 2(116GAG----UAG).

“…Freshly drawn blood was adjusted to a packed cell volume of 50% and incubated for i h at 370C in the presence of [3H]1-leucine under conditions previously detailed (27). The globin chains were separated by high performance liquid chromatography (HPLC) on large-pore C4 columns (Zydac Inc.) (28) and the radioactivity incorporated into a-and fl-globin chains was determined as previously described (27).…”

alpha-Thalassemia caused by an unstable alpha-globin mutant.

“…For example, Hb Bibba, an a138Leu-Pro mutant affecting the same a-helix, causes hemolytic anemia from birth (35). Furthermore, a highly unstable f3-globin mutant (Hb Indianapolis) associated with a fl-thalassemia phenotype is accompanied by hemolytic anemia in the heterozygous state (36). In distinction to these cases, the simple heterozygotes for the nondeletion defect (al2.5Proa/aa) in the family in the present study show no evidence of hemolysis or Heinz bodies, indicating that the mutant chain does not result in an unstable hemoglobin syndrome.…”