title: Molecular basis of hypoxanthine-guanine phosphoribosyltransferase deficiency in thirteen Spanish families.
abstract: We have determined the molecular basis of hypoxanthine-guanine phosphoribosyltransferase (HPRT; HPRT1) deficiency in eight Lesch-Nyhan patients and in five partially HPRT deficient patients with mild to severe neurologic symptoms. Eight of these thirteen mutations have not been previously described. HPRT Zaragoza II (a GG insertion in exon 2), HPRT Murcia (an AG deletion in exon 4), HPRT Asturias (a A deletion in exon 4) and HPRT Cartagena (a A insertion in exon 6) cause a frame-shift resulting in a premature stop codon. HPRT Sevilla is a splice-site mutation resulting in exon 8 skipping in the HPRT mRNA. HPRT Huelva, Madrid II and Zaragoza I are point mutations that result in single amino-acid changes in the mutated HPRT protein (118G-->A, G40R; 143G-->A, R 48 H; 397G-->A, V133 M, respectively). Three mutations have been previously described in unrelated families, and two mutations have been already published. All mutations that resulted in truncated proteins corresponded to patients with the Lesch-Nyhan phenotype. Characterization of the HPRT mutation allowed us to make carrier detection in 33 women and prenatal diagnosis in two fetuses. Hum Mutat 15:383, 2000.
authors.affiliation: Division of Clinical Biochemistry, Hospital La Paz, Universidad Autónoma, Madrid, Spain.
authors.forename: R J
authors.initials: RJ
authors.lastname: Torres
authors.forename: F A
authors.initials: FA
authors.lastname: Mateos
authors.forename: J
authors.initials: J
authors.lastname: Molano
authors.forename: B S
authors.initials: BS
authors.lastname: Gathoff
authors.forename: J P
authors.initials: JP
authors.lastname: O'Neill
authors.forename: R M
authors.initials: RM
authors.lastname: Gundel
authors.forename: L
authors.initials: L
authors.lastname: Trombley
authors.forename: J G
authors.initials: JG
authors.lastname: Puig
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D006580:Genetic Carrier Screening; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency* / Q000235:genetics*; D007926:Lesch-Nyhan Syndrome / Q000201:enzymology / Q000235:genetics; D016254:Mutagenesis, Insertional / Q000235:genetics; D017354:Point Mutation / Q000235:genetics; D011247:Pregnancy; D011296:Prenatal Diagnosis; D017384:Sequence Deletion / Q000235:genetics; D013030:Spain
chemical_list: D007041:Hypoxanthine Phosphoribosyltransferase