Abstract
A complete deficiency of hypoxanthine-guanine phosphoribosyl-transferase (HPRT) activity results in the Lesch-Nyhan syndrome. Of the 15 Lesch-Nyhan patients studied by Wilson et al. (1), HPRT cross-reactinq material (CRM) was detected in lymphoblasts from only four (1.3%, 50%, 72% and 92% of control concentrations) whereas 12 had HPRT-specific mRNA. None of the three patients lacking mRNA had detectable CRM. We have studied CRM levels in haemolysates and lymphoblast lysates from two Lesch-Nyhan patients (R.W. and J.G). In the first series of experiments, normal CRM levels were measured and lysates from both patients gave strong precipitation lines in immunodiffusion analysis. In the second series, using a different HPRT preparation in the radioimmunoassay (RIA), very low CRM levels (0.5% and 0.1%) were obtained, although strong precipitation lines were still observed on Ouchterlony plates.
A possible explanation for these discrepancies lies in a change in structure of normal HPRT which we have observed on storage, leading to a reduction in binding affinity for the antibody. The enzyme used in the first series of CRM determinations had been stored for an extended period, whereas enzyme used in the second series was freshly prepared. This explanation implies that the protein present in Lesch-Nyhan patients binds to the antibody with a lower affinity than does the normal enzyme (see also ref.2). These studies suggest that HPRT-like protein may be present in a higher percentage of Lesch-Nyhan patients than previously thought and may be present even when HPRT-specific mRNA cannot be detected, as in patient R.W.
1. Wilson, J.M., Stout, J.T., Palella, T.D., Davidson, B.L., Kelley, W.N. and Caskey, C.T. (1986) J.Clin.Invest. 77:188–195.
2. Wilson, J.M., Baugher, B.W., Landa. L. and Kelley, W.N. (1981) J.Biol.Chem. 256:10306-10312.
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Keough, D., Gordon, R., De Jersey, J. et al. 73 IS HPRT-LIKE PROTEIN PRESENT IN LESCH-NYHAN PATIENTS?. Pediatr Res 24, 123 (1988). https://doi.org/10.1203/00006450-198807000-00097
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DOI: https://doi.org/10.1203/00006450-198807000-00097