Phenotypic variation among seven members of one family with deficiency of hypoxanthine-guanine phosphoribosyltransferase.

ABSTRACT: We describe a family of seven boys affected by Lesch-Nyhan disease with various phenotypes. Further investigations revealed a mutation c.203T>C in the gene encoding HGprt of all members, with substitution of leucine to proline at residue 68 (p.Leu68Pro). Thus patients from this family display a wide variety of symptoms although sharing the same mutation. Mutant HGprt enzyme was prepared by site-directed mutagenesis and the kinetics of the enzyme revealed that the catalytic activity of the mutant was reduced, in association with marked reductions in the affinity towards phosphoribosylpyrophosphate (PRPP). Its Km for PRPP was increased 215-fold with hypoxanthine as substrate and 40-fold with guanine as substrate with associated reduced catalytic potential. Molecular modeling confirmed that t

SUBMITTER: Ceballos-Picot I 

PROVIDER: S-EPMC3830450 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature