title: Hypoxanthine-guanine phosphoribosylotransferase deficiency--the spectrum of Polish mutations.
abstract: Hypoxanthine-guanine phosphoribosyltransferase (HPRT; EC 2.4.2.8) deficiency (OMIM 308000) is an inborn error of purine metabolism. The defect causes three overlapping clinical syndromes: Lesch-Nyhan disease (LND; OMIM 300322), HPRT-related hyperuricaemia with neurologic dysfunction (HRND) and hyperuricaemia alone (HRH; OMIM 300322). During the period 1977-2007, 18 patients belonging to 12 Polish families and one Latvian family with HPRT deficiency have been identified. The majority of patients had a typical LND phenotype, three patients were classified as HRH and one patient as an intermediate phenotype (HRND). Genetic analysis revealed 12 different HPRT1 mutations, five of them being unique. In two typical Lesch-Nyhan families a novel single-base substitution, c.220T>G (p.Phe74Val), and a deletion of seven nucleotides, c.395_401del7 (p.Ile132LysfsX3), were found. Another novel single-base substitution, c.295T>G (p.Phe99Val), was identified in a patient with severe partial deficiency of HPRT with neurological dysfunction. In patients belonging to the HRH group, two transitions were detected: c.481G>A (p.Ala161Thr) and c.526C>T (p.Pro176Ser). Other mutations identified in Polish patients, c.131A>G (p.Asp44Gly), c.222C>A (p.Phe74Leu), c.385-1G>A (p.Asn129_Glu134del), c.482C>A (p.Ala161Glu), c.508C>T (p.Arg170Ter) and c.569G>A (p.Gly190Glu), have been reported previously in unrelated patients and are located within one of the clusters of hot spots of the HPRT1 gene (exons 3, 7 and 8). Patients with partial phenotypes presented mutations predicted to permit some degree of residual enzyme function (single-base substitutions). All mutations, except c.508C>T (p.Arg170Ter), were found in single families only, indicating the lack of any common mutation causing HPRT deficiency in Poland.
authors.affiliation: Department of Metabolic Diseases, Endocrinology and Diabetology, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730, Warsaw, Poland. ajurecka@gmail.com
authors.forename: A
authors.initials: A
authors.lastname: Jurecka
authors.forename: E
authors.initials: E
authors.lastname: Popowska
authors.forename: A
authors.initials: A
authors.lastname: Tylki-Szymanska
authors.forename: J
authors.initials: J
authors.lastname: Kubalska
authors.forename: E
authors.initials: E
authors.lastname: Ciara
authors.forename: Z
authors.initials: Z
authors.lastname: Krumina
authors.forename: J
authors.initials: J
authors.lastname: Sykut-Cegielska
authors.forename: E
authors.initials: E
authors.lastname: Pronicka
mesh_terms: D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency / Q000235:genetics*; D007844:Latvia; D007926:Lesch-Nyhan Syndrome / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D009154:Mutation; D010641:Phenotype; D011044:Poland
chemical_list: D007041:Hypoxanthine Phosphoribosyltransferase