Hemoglobin Terre Haute arginine beta 106. A posthumous correction to the original structure of hemoglobin Indianapolis.

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.