Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00492 (hypoxanthine-guanine phosphoribosyltransferase)
 2,385 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clonal and the autoradiographic assays for 6-thioguanine-resistant (TGr) T-lymphocytes (T-Lys) in human blood are reviewed. Studies of TGr colonies recovered from clonal assays show that the mutant T-Lys (i) are either helper (T4) or suppressor (T8) cells, (ii) possess stable TGr phenotypes, (iii) are deficient in hypoxanthine guanine phosphoribosyltransferase (HPRT), and (iv) have structural alterations in the hprt gene. TGr T-Ly mutant frequencies (Mfs) determined by clonal assays are of the order of 10(-6)-10(-5) for normal adults. Autoradiographically determined variant frequencies (Vfs) are also in this range for normal adults when lymphocytes are cryopreserved before study to remove 'phenocopies'. Cancer exposed to potentially mutagenic treatments have elevated TGr T-Ly Vfs. Comparative clonal and autoradiographic assays of the same blood samples give generally similar results when allowances are made for potential sources of error in each assay. The TGr T-Ly system is presented for human specific-locus mutagenicity monitoring.
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PMID:Somatic gene mutations in vivo as indicated by the 6-thioguanine-resistant T-lymphocytes in human blood. 387 12

5-Amino-4-imidazolecarboxamide riboside 5'-monophosphate (ZMP) is an intermediate in the purine de novo synthetic pathway that may be further metabolized to inosine 5'-monophosphate, degraded to the corresponding nucleoside (5-amino-4-imidazole-carboxamide riboside; Z-riboside), or phosphorylated to the corresponding 5'-triphosphate (ZTP). Accumulation of ZTP in microorganisms has been associated with depletion of folate intermediates that are necessary for the conversion of ZMP to inosine 5'-monophosphate and has been postulated to play a regulatory role in cellular metabolism. We have shown the presence of Z-nucleotides in erythrocytes derived from five individuals with the Lesch-Nyhan syndrome. Erythrocyte folate levels were within the normal range, although guanosine triphosphate levels were significantly reduced below those in normal controls (P less than 0.01). A small amount of Z-nucleotide accumulation was also found in one individual with partial deficiency of the enzyme hypoxanthine guanine phosphoribosyltransferase and in two individuals with other disorders of purine overproduction. In contrast, no Z-nucleotides were detected in 13 normal controls or in three individuals with hyperuricemia on allopurinol therapy. We conclude that Z-nucleotide formation may result from markedly increased rates of de novo purine biosynthesis. It is possible that metabolites of these purine intermediates may play a role in the pathogenesis of the Lesch-Nyhan syndrome.
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PMID:Z-nucleotide accumulation in erythrocytes from Lesch-Nyhan patients. 407 87

We report the results of carrier and prenatal diagnosis for hypoxanthine guanine phosphoribosyltransferase (HPRT) deficiency, Lesch-Nyhan syndrome, by carrier testing of 83 women and prenatal analysis of 26 pregnancies. Our diagnostic methodologies include mutation detection and linkage analysis for probands and their families and biochemical measurement of HPRT enzyme activity for at-risk pregnancies. Identification of the mutation in the index case of each family permits precise carrier diagnosis using polymerase chain reaction (PCR) amplification of HPRT gene sequences and automated DNA sequencing. We demonstrate 100 per cent sensitivity for the detection of mutations in the HPRT gene of affected males and highly efficient carrier testing of at-risk females. Two other molecular methods proven to have high utility include PCR-based dosage analysis and linkage analysis by PCR amplification of a short tandem repeat (STR) in intron 3 of the HPRT gene. As a result, 45 at-risk women, 56 per cent of those tested, were identified not to be carriers of their family's HPRT gene mutation. Seven of these women were the mothers of affected males and prenatal testing for future pregnancies was recommended because of the possibility of gonadal mosaicism. Thirty-eight of these women were more distant relatives of affected males, thereby eliminating the need for future prenatal procedures. These studies illustrate the utility and precision of molecular methodologies for carrier and prenatal diagnosis of Lesch-Nyhan syndrome. These studies also illustrate that molecular diagnostic studies of affected males and carrier testing prior to pregnancy can clarify genetic risk predictions and eliminate unnecessary prenatal procedures.
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PMID:Lesch-Nyhan syndrome: carrier and prenatal diagnosis. 761 74

Complete deficiency of hypoxanthine guanine phosphoribosyltransferase (HPRT) causes Lesch-Nyhan syndrome. A single nucleotide substitution of G to T at the 3'-end of intron 3 in the splicing consensus region has been identified in one allele of the HPRT gene from a mother predicted to be a heterozygous Lesch-Nyhan carrier. Utilizing a BfaI restriction site which was lost in the mutation as an indicator, family study showed that the mother and her only daughter were heterozygotes but the mother's sister did not have the mutant allele. The mutation generated splicing error and resulted in two types of abnormal mRNA. The major altered mRNA, named Type I, skipped the exon 4 and is predicted to produce a protein deleted of 22 amino acid residues. The other, Type II, having a 9-bp deletion at the 5'-end of exon 4, can result in a protein lacking 3 amino acids, from codon 107 to 109.
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PMID:Molecular genetic study of a Japanese family with Lesch-Nyhan syndrome: a point mutation at the consensus region of RNA splicing (HPRTKeio). 818 19

The distributional and activity changes of hypoxanthine guanine phosphoribosyltransferase (HGPRT) were investigated in the developing mouse brain. The HGPRT activity level was low at birth, increased rapidly during the first 7 days of life, and underwent a gradual increase thereafter to the mature level. Polyclonal antibody against HGPRT purified from mouse brain was prepared for immunohistochemical demonstration of the enzyme during brain development. In the cerebellum, part of the Purkinje cells was consistently immunostained throughout growth, and the presence of HGPRT was observed in the dendrites of mature Purkinje cells. The most dominant change in HGPRT localization was observed in the hippocampus. Little HGPRT was detectable in the newborn mouse hippocampus. At postnatal day 7, cytoplasmic HGPRT appeared sporadically in the granular cells independently of the region of the hippocampus. The number of positive immunoreactive cells increased with growth, and the dendrites of granular cells were also immunostained on postnatal day 28. Further immunostaining was noted in the granule cells of the dentate gyrus on postnatal day 35. The above results suggest that HGPRT may play an important role in the developing hippocampus. Further investigations of the HGPRT in the human hippocampus may help to clarify the mechanism underlying the neurological disorders encountered in the Lesch-Nyhan syndrome.
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PMID:Postnatal expression of hypoxanthine guanine phosphoribosyltransferase in the mouse brain. 819 72

Complete deficiency of hypoxanthine guanine phosphoribosyltransferase (HPRT) causes Lesch-Nyhan syndrome. We examined the HPRT gene mutation for prenatal diagnosis in a Japanese family. A single nucleotide substitution of C to T in exon 3 was identified by direct sequencing analysis of the HPRT gene of a Lesch-Nyhan patient. This substitution resulted in a nonsense mutation, CGA (Arg) to TGA (stop), at codon 51. Utilizing an Xho I restriction site which was lost in the mutation as an indicator, a family study showed that the mother was heterozygous, but the grandmother normal. By the same method, prenatal genetic diagnosis was performed using chorionic villus samples (CVS), and showed that the fetus had the mutant allele.
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PMID:Molecular analysis of a Japanese family with Lesch-Nyhan syndrome: identification of mutation and prenatal diagnosis. 894 18

A virtually complete deficiency of hypoxanthine guanine phosphoribosyltransferase (HPRT) causes Lesch-Nyhan syndrome. A novel mutation of HPRT gene in a Japanese Lesch-Nyhan family has been identified using mRNA and genomic DNA from peripheral blood cells. A single nucleotide substitution of T to C in exon 3 resulted in a mis-sense mutation, CTC (Leu) to CCC (Pro), at codon 65. Utilizing an Mn/I restriction site which was lost in the mutation as an indicator, a family study showed that the mother was normal not having the mutant gene. The mutation was a de novo event that had occurred in the germ cells of the mother or in the proband during the early phase of fetal development.
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PMID:A novel de novo mutation in HPRT gene responsible for Lesch-Nyhan syndrome (HPRT OSAKA). 908 15

Different degrees of hypoxanthine guanine phosphoribosyltransferase (HPRT) deficiency are associated with hyperuricemia, uric acid nephrolithiasis and severe gout. Up to 25-30% of HPRT deficient patients, indicated as neurological variants or HPRT-related hyperuricemia with neurological dysfunction (HRND), may develop neurological manifestation, from mild to severe; the most serious ones manifesting in the devastating Lesch-Nyhan syndrome, characterized by choreoathetosis or self-mutilation. Here we present a 30 years old male patient suffering from gout and mild psycho-motor impairment without Lesch Nyhan disease despite severe HPRT deficiency residual activity 0.02% with hypoxanthine, no activity at all with guanine as a substrate. The Curto's theory that neurologic impairment is dependent on VGPRT/VHPRT ratio is not confirmed by our observations. The finding of such a severe HPRT deficiency in a non-Lesch-Nyhan patient needs further investigation. G6PD deficiency was also referred together with beta-thalassemic trait. We have studied purine and pyridine nucleotide metabolism in the erythrocytes and discussed the literature. The bone marrow sample shows a megaloblastyc aspect.
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PMID:Kelley-Seegmiller syndrome in a patient with complete hypoxanthine-guanine phosphoribosyltransferase deficiency. 1250 81

Inherited mutation of hypoxanthine guanine phosphoribosyltransferase, (HPRT) gives rise to Lesch-Nyhan syndrome or HPRT-related gout. We have identified 34 mutations in 28 Japanese, 7 Korean, and 1 Indian families with the patients manifesting different clinical phenotypes, including two rare cases in female subjects, by the analysis of all nine exons of HPRT from the genomic DNA and reverse transcribed mRNA using PCR technique coupled with direct sequencing.
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PMID:Mutations in the hypoxanthine guanine phosphoribosyltransferase gene (HPRT1) in Asian HPRT deficient families. 1557 Dec 23

Inherited mutations of a purine salvage enzyme, hypoxanthine guanine phosphoribosyltransferase (HPRT, EC 2.4.2.8), give rise to Lesch-Nyhan syndrome or HPRT-related gout. We have identified a number of HPRT mutations in Asian patients manifesting different clinical phenotypes, by analyzing all nine exons of the HPRT gene (HPRT1) from genomic DNA and reverse-transcribed mRNA using the PCR technique coupled with direct sequencing. In this study, we update the spectrum of mutations with nine novel mutations. Two missense mutations (T124P and D185G) were detected in patients with HRH (HPRT-related hyperuricemia). In a patient having a severe partial deficiency of HPRT with neurological dysfunction (HRND: HPRT-related neurological dysfunction), a single nucleotide substitution (27+5G > A) causing a splicing error was found in intron 1. The mutation resulted in a remarkably decreased level of normal mRNA, and production of an abnormal mRNA with a 49-bp insert at the 5'-end of intron 1, which caused the frame-shift of an amino acid codon (10fs27X). In six typical Lesch-Nyhan families, we found two 3-bp deletions responsible for single amino acid deletions (V8del and Y28del), two 1-bp deletions (440delA and 635delG) generating a frame-shift, an insertion of two amino acids (159insKV), and a 4,131-bp deletion from introns 4 to 6 resulting in two types of abnormal mRNA. Including these nine mutations, 42 HPRT1 mutations have been identified among 47 Asian families with deficiency of HPRT.
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PMID:Molecular analysis of HPRT deficiencies: an update of the spectrum of Asian mutations with novel mutations. 1702 11


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