The initial report of
Hb Indianapolis described two affected individuals with the phenotype of severe
beta-thalassemia that was dominantly inherited. The structure of this variant could not be deduced by standard techniques because of its extreme instability. Because of this limitation, the structure was ascertained by analysis of the abnormal
globin chain, which had been radioactively labeled. These studies strongly suggested that the structure of this variant was
cysteine beta 112 to
arginine. Subsequent to this report, two additional families with
Hb Indianapolis were found. The carriers were minimally affected and the abnormal
hemoglobin was only mildly unstable. This major difference in phenotypic expression suggested that further investigation of the original family should be carried out. Unfortunately, both of the original carriers of the variant succumbed to their severe
anemia prior to the subsequent reports. However, by the use of the polymerase chain reaction, enough
DNA was obtained to sequence the third exon of the
beta-globin gene in the original family from the
DNA scraped off a 10-year-old bone marrow microscope slide. These studies revealed a substitution of
leucine to
arginine at position 106 of the
beta-globin chain. The polymerase chain reaction results may be consistent with the original
protein structural data, if incomplete tryptic cleavage of this
arginine residue occurred in the original sample. We have renamed this variant
Hb Terre Haute in an attempt to avoid
confusion with the Cys beta 112----Arg substitution.