title: Partial HPRT deficiency phenotype and incomplete splicing mutation.
abstract: Deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity is an inborn error of purine metabolism associated with uric acid overproduction and a continuum spectrum of neurological manifestations depending on the degree of enzyme deficiency. The complete deficiency causes Lesch-Nyhan syndrome (LNS). Partial HPRT-deficient patients can show a variable degree of neurological manifestations. Both diseases have been associated with mutations in the HPRT1 gene. Documented mutations in HPRT deficiency show a high degree of heterogeneity in type and location within the gene. In fact, more than 300 disease-associated mutations have been described. Splice mutations accounts for more that 16% of HPRT mutations and in most cases cause a complete LNS phenotype. A 16 year-old boy consulted to La Paz University Hospital because of hyperuricemia (9.4 mg/dL). At age one year he was given a diagnosis of dystonic cerebral palsy. Although he usually employs a wheelchair, under certain circumstances, he is able to stand up and walk by himself. He has never showed self injurious behavior. This patient presented a splice mutation (NM_000194.2: c.552 -2 A > G) causing exon 5 exclusion. An exon-5 specific PCR was designed, and a minor amount of normally spliced HPRT mRNA was found. Normally spliced HPRT mRNA was quantified by real-time PCR in this patient, in control subjects, and in two Lesch Nyhan patient with splice mutations excluding exon 4 (patient B) and exon 8 (patient C) who had clinically a Lesch Nyhan disease phenotype. A minor amount of normally spliced HPRT mRNA was found in all the patients. No correlation was found between the percentage of the normally spliced HPRT mRNA and the phenotype. We conclude that the partial HPRT deficient phenotype of this patient can not be explained by the finding of a minor amount of normally splice HPRT mRNA. It is possible that the amount of normally splice mRNA vary among different tissues.
authors.affiliation: Divisions of Clinical Biochemistry and Internal Medicine, La Paz University Hospital, Madrid, Spain. rtorres.hulp@salud.madrid.org
authors.forename: R J
authors.initials: RJ
authors.lastname: Torres
authors.forename: M G
authors.initials: MG
authors.lastname: Garcia
authors.forename: J G
authors.initials: JG
authors.lastname: Puig
mesh_terms: D000293:Adolescent; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency* / Q000235:genetics*; D007926:Lesch-Nyhan Syndrome / Q000235:genetics* / Q000473:pathology; D008297:Male; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D012326:RNA Splicing / Q000235:genetics*
chemical_list: D007041:Hypoxanthine Phosphoribosyltransferase