Scientific background:

Summary: The enzyme encoded by this gene plays a central role in the generation of purine nucleotides through the purine salvage pathway. Mutations in this gene result in X-linked recessive Lesch-Nyhan syndrome or gout.

Methodology:

	clinical test	Method		Genomic sequencing of the entire coding region
		Turn-around time		25 working days
		Effort		little
		Specimen		DNA
		Quality assessment		Internal quality control only
	All known and new missense, nonsense and splice mutations can be detected.
	clinical test	Method		Carrier testing
		Turn-around time		5 working days
		Effort		little
		Specimen		DNA
		Quality assessment		Internal quality control only
	The test is only specific about the mutation already known in this kindred.

Literature: 

Aral B et al. (1996) Novel nonsense mutation in the hypoxanthine guanine phosphoribosyltransferase gene and nonrandom X-inactivation causing Lesch-Nyhan syndrome in a female patient.
Benke PJ et al. (1973) In vitro effects of magnesium ions on mutant cells from patients with the Lesch-Nyhan syndrome.
Benke PJ et al. (1973) Hypoxanthine-guanine phosphoribosyltransferase variant associated with accelerated purine synthesis.
Boyd M et al. (1993) Screening for molecular pathologies in Lesch-Nyhan syndrome.
Brennand J et al. (1982) Cloned cDNA sequences of the hypoxanthine/guanine phosphoribosyltransferase gene from a mouse neuroblastoma cell line found to have amplified genomic sequences.
Cariello NF et al. (1988) Resolution of a missense mutant in human genomic DNA by denaturing gradient gel electrophoresis and direct sequencing using in vitro DNA amplification: HPRT Munich.
Caskey CT et al. (1979) The HPRT locus.
Colgin LM et al. (2002) The unexpected landscape of in vivo somatic mutation in a human epithelial cell lineage.
Cox RP et al. (1970) Evidence for transfer of enzyme product as the basis of metabolic cooperation between tissue culture fibroblasts of Lesch-Nyhan disease and normal cells.
Dancis J et al. (1973) Disparate enzyme activity in erythocytes and leukocytes. A variant of hypoxanthine phosphoribosyl-transferase deficiency with an unstable enzyme.
Davidson BL et al. (1988) Hypoxanthine-guanine phosphoribosyltransferase. Genetic evidence for identical mutations in two partially deficient subjects.
Davidson BL et al. (1989) Human hypoxanthine-guanine phosphoribosyltransferase deficiency. The molecular defect in a patient with gout (HPRTAshville).
Davidson BL et al. (1988) Genetic basis of hypoxanthine guanine phosphoribosyltransferase deficiency in a patient with the Lesch-Nyhan syndrome (HPRTFlint).
Davidson BL et al. (1989) Molecular basis of hypoxanthine-guanine phosphoribosyltransferase deficiency in ten subjects determined by direct sequencing of amplified transcripts.
Davidson BL et al. (1991) Identification of 17 independent mutations responsible for human hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency.
De Gregorio L et al. (2000) An unexpected affected female patient in a classical Lesch-Nyhan family.
DeMars R et al. (1969) Lesch-Nyhan mutation: prenatal detection with amniotic fluid cells.
Dempsey JL et al. (1983) Detection of the carrier state for an X-linked disorder, the Lesch-Nyhan syndrome, by the use of lymphocyte cloning.
Dobrovic A et al. (1987) A HindIII RFLP for the HPRT pseudogene on chromosome 3 (HPRTP1).
Doetschman T et al. () Targetted correction of a mutant HPRT gene in mouse embryonic stem cells.
Edwards A et al. (1990) Automated DNA sequencing of the human HPRT locus.
Emmerson BT et al. (1972) Partial deficiency of hypoxanthine-guanine phosphoribosyltransferase: intermediate enzyme deficiency in heterozygote red cells.
Emmerson BT et al. (1974) Absence of measurable linkage between the loci for hypoxanthine-guanine phosphoribosyltransferase and deutan colorblindness.
Engle SJ et al. (1996) HPRT-APRT-deficient mice are not a model for lesch-nyhan syndrome.
Epstein CJ et al. (1972) Expression of the mammalian X chromosome before and after fertilization.
Ernst M et al. (1996) Presynaptic dopaminergic deficits in Lesch-Nyhan disease.
Fenwick RG et al. (1980) Reversion of a mutation affecting the molecular weight of HGPRT: intragenic suppression and localization of X-linked genes.
Fox IH et al. (1975) Hypoxanthine-guanine phosphoribosyltransferase. Characterization of a mutant in a patient with gout.
Francke U et al. (1974) Linkage relationships of X-linked enzymes glucose-6-phosphate dehydrogenase and hypoxanthine guanine phosphoribosyltransferase: recombination in female offspring of compound heterozygotes.
Francke U et al. (1976) The occurrence of new mutants in the X-linked recessive Lesch-Nyhan disease.
Francke U et al. (1977) Answer to criticism of Morton and Lalouel.
Francke U et al. (1979) Assignment of the gene for cytoplasmic superoxide dismutase (Sod-1) to a region of chromosome 16 and of Hprt to a region of the X chromosome in the mouse.
Fujimori S et al. (1989) Identification of a single nucleotide change in the hypoxanthine-guanine phosphoribosyltransferase gene (HPRTYale) responsible for Lesch-Nyhan syndrome.
Fujimori S et al. (1988) Identification of a single nucleotide change in a mutant gene for hypoxanthine-guanine phosphoribosyltransferase (HPRT Ann Arbor).
Fujimori S et al. (1990) Hypoxanthine guanine phosphoribosyltransferase deficiency: nucleotide substitution causing Lesch-Nyhan syndrome identified for the first time among Japanese.
Fujimori S et al. (1992) A germ line mutation within the coding sequence for the putative 5-phosphoribosyl-1-pyrophosphate binding site of hypoxanthine-guanine phosphoribosyltransferase (HPRT) in a Lesch-Nyhan patient: missense mutations within a functionally important region probably cause disease.
Gartler SM et al. (1975) Half chromatid mutations: transmission in humans?
Gibbs RA et al. (1987) Identification and localization of mutations at the Lesch-Nyhan locus by ribonuclease A cleavage.
Gibbs RA et al. (1990) Multiplex DNA deletion detection and exon sequencing of the hypoxanthine phosphoribosyltransferase gene in Lesch-Nyhan families.
Gibbs RA et al. (1989) Identification of mutations leading to the Lesch-Nyhan syndrome by automated direct DNA sequencing of in vitro amplified cDNA.
Gordon RB et al. (1991) The molecular characterisation of HPRT CHERMSIDE and HPRT COORPAROO: two Lesch-Nyhan patients with reduced amounts of mRNA.
Gordon RB et al. (1990) Identification of a single nucleotide substitution in the coding sequence of in vitro amplified cDNA from a patient with partial HPRT deficiency (HPRTBRISBANE).
Goss SJ et al. (1977) Gene transfer by means of cell fusion I. Statistical mapping of the human X-chromosome by analysis of radiation-induced gene segregation.
Graham GW et al. (1996) Prenatal diagnosis by enzyme analysis in 15 pregnancies at risk for the Lesch-Nyhan syndrome.
Greene ML et al. (1972) Clinical features of patients with the "partial" deficiency of the X-linked uricaciduria enzyme.
Greene ML et al. (1970) Hypoxanthine-guanine phosphoribosyltransferase deficiency and Xg blood group.
Gutensohn W et al. (1979) Partial deficiency of hypoxanthine-phosphoribosyltransferase:evidence for a structural mutation in a patient with gout.
Hashimi S et al. (1976) Further evidence of X-linkage of hypoxanthine phosphoribosyl-transferase in the mouse.
Henderson JF et al. (1969) Inheritance of purine phosphoribosyltransferases in man.
HOEFNAGEL D et al. (1965) HEREDITARY CHOREOATHETOSIS, SELF-MUTILATION AND HYPERURICEMIA IN YOUNG MALES.
Holland PC et al. (1983) Hypoxanthine guanine phosphoribosyl transferase deficiency presenting with gout and renal failure in infancy.
Hooper M et al. () HPRT-deficient (Lesch-Nyhan) mouse embryos derived from germline colonization by cultured cells.
Jolly DJ et al. (1982) Isolation of a genomic clone partially encoding human hypoxanthine phosphoribosyltransferase.
Jolly DJ et al. (1983) Isolation and characterization of a full-length expressible cDNA for human hypoxanthine phosphoribosyl transferase.
Keebaugh AC et al. (2007) Gene duplication and inactivation in the HPRT gene family.
Kelley WN et al. (1969) Hypoxanthine-guanine phosphoribosyltransferase deficiency in gout.
Kelley WN et al. (1967) A specific enzyme defect in gout associated with overproduction of uric acid.
Kim SH et al. (1986) The organization of the human HPRT gene.
Kogut MD et al. (1970) Disorder of purine metabolism due to partial deficiency of hypoxanthine-guanine phosphoribosyltransferase. A study of a family.
Koller BH et al. (1989) Germ-line transmission of a planned alteration made in a hypoxanthine phosphoribosyltransferase gene by homologous recombination in embryonic stem cells.
Kuehn MR et al. () A potential animal model for Lesch-Nyhan syndrome through introduction of HPRT mutations into mice.
LESCH M et al. (1964) A FAMILIAL DISORDER OF URIC ACID METABOLISM AND CENTRAL NERVOUS SYSTEM FUNCTION.
Lightfoot T et al. (1992) The point mutation of hypoxanthine-guanine phosphoribosyltransferase (HPRTEdinburgh) and detection by allele-specific polymerase chain reaction.
Lightfoot T et al. (1994) Sequence, expression and characterization of HPRTMoose Jaw: a point mutation resulting in cooperativity and decreased substrate affinities.
Lloyd KG et al. (1981) Biochemical evidence of dysfunction of brain neurotransmitters in the Lesch-Nyhan syndrome.
Malleson PN et al. (1996) The incidence of pediatric rheumatic diseases: results from the Canadian Pediatric Rheumatology Association Disease Registry.
Marcus S et al. (1992) Mutation analysis and prenatal diagnosis in a Lesch-Nyhan family showing non-random X-inactivation interfering with carrier detection tests.
McDonald JA et al. (1971) Lesch-Nyhan syndrome: altered kinetic properties of mutant enzyme.
McDonald JA et al. (1972) Lesch-Nyhan syndrome: absence of the mutant enzyme in erythrocytes of a heterozygote for both normal and mutant hypoxanthine-guanine phosphoribosyl transferase.
McKeran RO et al. (1975) The diagnosis of the carrier state for the Lesch--Nyhan syndrome.
Melton DW et al. (1984) Structure, expression, and mutation of the hypoxanthine phosphoribosyltransferase gene.
Migeon BR et al. (1970) X-linked hypoxanthine-guanine phosphoribosyl transferase deficiency: detection of heterozygotes by selective medium.
Migeon BR et al. (1968) X-linked hypoxanthine-guanine phosphoribosyl transferase deficiency: heterozygote has two clonal populations.
Miller AD et al. (1983) A transmissible retrovirus expressing human hypoxanthine phosphoribosyltransferase (HPRT): gene transfer into cells obtained from humans deficient in HPRT.
Mizunuma M et al. (2001) A recurrent large Alu-mediated deletion in the hypoxanthine phosphoribosyltransferase (HPRT1) gene associated with Lesch-Nyhan syndrome.
Monk M et al. (1990) Preimplantation sexing and diagnosis of hypoxanthine phosphoribosyl transferase deficiency in mice by biochemical microassay.
Monnat RJ et al. (1992) Molecular structure and genetic stability of human hypoxanthine phosphoribosyltransferase (HPRT) gene duplications.
Morton NE et al. (1977) Genetic epidemiology of Lesch-Nyhan disease.
Myers RM et al. (1985) Detection of single base substitutions by ribonuclease cleavage at mismatches in RNA:DNA duplexes.
Nabholz M et al. (1969) Genetic analysis with human--mouse somatic cell hybrids.
Newcombe DS et al. (1966) Treatment of x-linked primary hyperuricemia with allopurinol.
Nussbaum RL et al. (1983) A three-allele restriction-fragment-length polymorphism at the hypoxanthine phosphoribosyltransferase locus in man.
Nyhan WL et al. (1970) Hemizygous expression of glucose-6-phosphate dehydrogenase in erythrocytes of heterozygotes for the Lesch-Nyhan syndrome.
Nyhan WL et al. (1996) New approaches to understanding Lesch-Nyhan disease.
Ogasawara N et al. (1989) Molecular analysis of a female Lesch-Nyhan patient.
Pai GS et al. (1980) Localization of loci for hypoxanthine phosphoribosyltransferase and glucose-6-phosphate dehydrogenase and biochemical evidence of nonrandom X chromosome expression from studies of a human X-autosome translocation.
Patel PI et al. (1986) Fine structure of the human hypoxanthine phosphoribosyltransferase gene.
Renwick PJ et al. (1995) Southern analysis reveals a large deletion at the hypoxanthine phosphoribosyltransferase locus in a patient with Lesch-Nyhan syndrome.
Rijksen G et al. (1981) Partial hypoxanthine-guanine phosphoribosyl transferase deficiency with full expression of the Lesch-Nyhan syndrome.
Rosenbloom FM et al. (1967) Inherited disorder of purine metabolism. Correlation between central nervous system dysfunction and biochemical defects.
Rosenstraus M et al. (1975) Isolation of mammalian cell mutants deficient in glucose-6-phosphate dehydrogenase activity: linkage to hypoxanthine phosphoribosyl transferase.
Ruddle FH et al. () Linkage studies employing mouse--man somatic cell hybrids.
Sass JK et al. (1965) Juvenile gout with brain involvement.
Sculley DG et al. (1991) Hypoxanthine-guanine phosphoribosyltransferase deficiency: analysis of HPRT mutations by direct sequencing and allele-specific amplification.
Sculley DG et al. (1992) A review of the molecular basis of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency.
Seegmiller JE et al. (1989) Contributions of Lesch-Nyhan syndrome to the understanding of purine metabolism.
Seegmiller JE et al. (1967) Enzyme defect associated with a sex-linked human neurological disorder and excessive purine synthesis.
Shapiro SL et al. (1966) X-linked recessive inheritance of a syndrome of mental retardation with hyperuricemia.
Shows TB et al. (1975) Human X-Linked genes regionally mapped utilizing X-autosome translocations and somatic cell hybrids.
Silvers DN et al. (1972) Detection of heterozygote in Lesch-Nyhan disease by hair-root analysis.
Simpson D et al. (1988) A method for specific cloning and sequencing of human hprt cDNA for mutation analysis.
Sinnett D et al. (1988) Lesch-Nyhan syndrome: molecular investigation of three French Canadian families using a hypoxanthine-guanine phosphoribosyltransferase cDNA probe.
Skopek TR et al. (1990) Molecular analyses of a Lesch-Nyhan syndrome mutation (hprtMontreal) by use of T-lymphocyte cultures.
Snyder FF et al. (1984) Partial deficiency of hypoxanthine-guanine phosphoribosyltransferase with reduced affinity for PP-ribose-P in four related males with gout.
Snyder FF et al. (1989) Hypoxanthine-guanine phosphoribosyltransferase deficiency in three brothers with gout: characterization of a variant, HPRTEdinburgh, having altered isoelectric point, increased thermal lability and normal levels of messenger RNA.
Srivastava T et al. (2002) Childhood hyperuricemia and acute renal failure resulting from a missense mutation in the HPRT gene.
Stout JT et al. (1985) HPRT: gene structure, expression, and mutation.
Strauss GH et al. (1980) An enumerative assay of purine analogue resistant lymphocytes in women heterozygous for the Lesch-Nyhan Mutation.
Strauss M et al. (1981) HGPRT structural gene mutation in Lesch-Nyhan-syndrome as indicated by antigenic activity and reversion of the enzyme deficiency.
Tarlé SA et al. (1991) Determination of the mutations responsible for the Lesch-Nyhan syndrome in 17 subjects.
Toyo-Oka T et al. (1975) X-linked hypoxanthine-guanine phosphoribosyltransferase deficiency without neurological disorders. a report of a family.
van Bogaert P et al. (1992) Lesch-Nyhan syndrome in a girl.
Vogel F et al. (1977) A probable sex difference in some mutation rates.
Willers I et al. (1977) Genetic heterogeneity of hypoxanthine-phosphoribosyl transferase in human fibroblasts of 3 families.
Wilson JM et al. (1981) Human hypoxanthine-guanine phosphoribosyltransferase. Purification and characterization of mutant forms of the enzyme.
Wilson JM et al. (1982) Human hypoxanthine-guanine phosphoribosyltransferase. Demonstration of structural variants in lymphoblastoid cells derived from patients with a deficiency of the enzyme.
Wilson JM et al. (1983) Human hypoxanthine-guanine phosphoribosyltransferase. Detection of a mutant allele by restriction endonuclease analysis.
Wilson JM et al. (1983) Molecular basis of hypoxanthine-guanine phosphoribosyltransferase deficiency in a patient with the Lesch-Nyhan syndrome.
Wilson JM et al. (1984) Human hypoxanthine-guanine phosphoribosyltransferase. Structural alteration in a dysfunctional enzyme variant (HPRTMunich) isolated from a patient with gout.
Wilson JM et al. (1983) Human hypoxanthine-guanine phosphoribosyltransferase.
Wilson JM et al. (1986) A molecular survey of hypoxanthine-guanine phosphoribosyltransferase deficiency in man.
Wilson JM et al. (1983) Human hypoxanthine (guanine) phosphoribosyltransferase: an amino acid substitution in a mutant form of the enzyme isolated from a patient with gout.
Wilson JM et al. (1983) Hypoxanthine-guanine phosphoribosyltransferase deficiency. The molecular basis of the clinical syndromes.
Winter RM et al. (1980) Estimation of male to female ratio of mutation rates from carrier-detection tests in X-linked disorders.
Wong DF et al. (1996) Dopamine transporters are markedly reduced in Lesch-Nyhan disease in vivo.
Wu CL et al. (1993) Production of a model for Lesch-Nyhan syndrome in hypoxanthine phosphoribosyltransferase-deficient mice.
Yang TP et al. () Molecular evidence for new mutation at the hprt locus in Lesch-Nyhan patients.
Yang TP et al. (1988) Spontaneous reversion of novel Lesch-Nyhan mutation by HPRT gene rearrangement.
Yü TF et al. (1972) Rarity of X-linked partial hypoxanthine-guanine phosphoribosyltransferase deficiency in a large gouty population.
Zannis VI et al. (1980) Characterization of the subunit composition of HGPRTase from human erythrocytes and cultured fibroblasts.
Zoref E et al. (1979) Increased de novo purine synthesis in cultured skin fibroblasts from heterozygotes for the Lesch-Nyhan syndrome. A sensitive marker for carrier detection.
Zoref-Shani E et al. (2000) Kelley-Seegmiller syndrome due to a unique variant of hypoxanthine-guanine phosphoribosyltransferase: reduced affinity for 5-phosphoribosyl-1-pyrophosphate manifested only at low, physiological substrate concentrations.