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 existence of a clinically typical Lesch-Nyhan syndrome was observed in a male infant with 18q deletion syndrome. Indirect hypoxanthine-guanine-phosphoribosyl transferase activity determination demonstrated a normal value, and thus the possibility of Lesch-Nyhan syndrome linked to the X-chromosome may be excluded. It is assumed that the uric acid metabolism must be under the primary or secondary effect of one or other of the gene loci on the long arm of chromosome 18, since the existence off a hyperuricaemic syndrome was observed in this 18q deletion patient.
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PMID:Hyperuricaemia associated with 18q deletion. Atypical Lesch-Nyhan syndrome? 697 10

Human diploid fibroblasts serially cultured in vitro show a progressive decline in their proliferative capacity. Much before the cells cease to divide, changes in certain phenotypic parameters can also be detected with passage level. A progressive decline in the ratio of two enzyme activities in the purine salvage pathway, one an X-linked enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and the other a biochemically related autosomal-linked enzyme, adenine phosphoribosyltransferase (APRT) becomes apparent with increasing population doublings. The more extensive relative decline in HGPRT activity with passage may be explained on gene dosage effects subsequent to the random inactivation of one X-chromosome in the somatic cells of mammalian females; however, other interpretations can be considered. Since the enzyme activity ratio of HGPRT/APRT decreases linearly with population doubling, it could be useful for the evaluation of the biological "age" of serially passaged cultures. Studies of X-linked processes in human diploid cells and its variations during the life-span in culture may contribute to our understanding of some of the mechanisms of "senescence/change" and of the etiology of certain maturity onset disorders.
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PMID:X-linked processes in serially passaged "aging" human diploid cells. 720 94

Somatic cell mutant frequencies at the hprt locus of the X-chromosome were measured with the T-lymphocyte cloning assay in a healthy pediatric population. Assays were performed on 49 subjects (29 males and 20 females) ranging in age from 0.08 to 15.2 years. A statistical analysis of the thioguanine-resistant (TGr) mutant frequency (MF), unselected cloning efficiency (CE) and age was performed using data obtained in this study and those previously obtained in our laboratory on 66 newborn umbilical cord blood samples and 230 adult blood samples. For statistical comparisons pediatric subjects were divided into 4 groups. Group I included cord blood samples (age 0 years); Group II were subjects between 0 and 5 years; Group III were between 6 and 11 years and Group IV were between 12 and 17 years. The ln MF of Groups I and II were significantly lower than Groups III and IV (p < 0.05). The mean ln MF for each of Groups I-IV was significantly lower than the adult value. The cloning efficiency for Group I was significantly lower than that for Groups II-IV and adults. The relationships among the ln MF, unselected CE and age were expressed by the equations: ln (MF) = 0.945 -2.453 CE (p < 0.001) and ln (MF) = 0.114 + 0.063 age (p 0.004). The slope coefficients for unselected CE and age were significantly different from adults (p < 0.05). Regression analysis of combined data from Groups I-IV and adults were performed using both age and unselected CE as well as terms to reflect differences in their relationships with ln MF in adults and children. The results showed that the intercept and the age coefficients differ significantly for children and adults after adjustment for CE and yielded the following equations: ln (MF) = 0.548 -1.676 CE + 0.075 age, (Groups I-IV) and ln (MF) = 2.263 -1.676 CE + 0.014 age (adults). An alternative statistical model using ln (age ), ln (MF) = 0.381 -1.767 CE + 0.673 ln (age + 1), (p < 0.001), describes the rapid increase in MF with age that levels off in late adolescence. These findings demonstrate the changing influence of age on mutant frequency in the pediatric population as compared to the adult populations. These studies also illustrate that the increase in background somatic mutant frequencies at the hprt locus in T-lymphocytes is not linear from birth to adolescence and is significantly different from that seen in the adult population.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Determination of hprt mutant frequencies in T-lymphocytes from a healthy pediatric population: statistical comparison between newborn, children and adult mutant frequencies, cloning efficiency and age. 751 49

Whole genomic hprt clones were used in Southern analysis to screen the integrity of the hprt gene in a family that includes a patient with HPRT enzyme deficiency causal to Lesch-Nyhan syndrome. A 5 kb DNA sequence deletion was found to have its endpoints in the first and third introns. The probes identified the carrier status of female family members, aided by an RFLP carried by the mother's normal X-chromosome.
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PMID:Southern analysis reveals a large deletion at the hypoxanthine phosphoribosyltransferase locus in a patient with Lesch-Nyhan syndrome. 758 56

Somatic cell mutant frequencies at the hprt locus of the X-chromosome were measured with the T-lymphocyte cloning technique in healthy human populations. A statistical analysis was performed of assays from 232 individuals (77 males and 155 females) ranging in age from 19 to 80 years. Data from 4 donor groups were compiled: (a) 132 participants in a study of identical and fraternal twins; (b) 17 health care workers studied as part of an assessment of the risks of handling chemotherapeutic drugs; (c) 62 women with benign breast masses; and (d) 21 normal laboratory and office personnel. The relationship between age and mutant frequency (MF) was expressed by the equation: ln MF = 1.46 + 0.018 age (P < 0.001). Thus, MF increased by about 2% per year. Increases in cloning efficiency (CE) reduced the MF, as shown in the equation: ln MF = 2.91 - 1.32 CE (P < 0.001). CE was significantly related to age (CE = 0.47 - 0.002 age, P = 0.038), and the interdependent relationship between MF, age and CE expressed by the equation: ln MF = 1.99 - 1.13 CE + 0.016 age was significant at the P < 0.001 level. There was no statistically significant effect of donor gender or smoking history on MF in our population, but CE was significantly lower in males (P < 0.001). These findings confirm the importance of age and CE as factors which influence the thioguanine-resistant MF in circulating T-lymphocytes from normal adults.
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PMID:Measurement of HPRT mutant frequencies in T-lymphocytes from healthy human populations. 767

The restriction fragment length polymorphisms (RFLP) of the X-chromosome phosphoglycerate kinase (PGK) and hypoxanthine phosphoribosyltransferase (HPRT) genes were used to study the clonal basis of the chronic myeloproliferative disorders (CMPD). Analyses were performed on granulocyte and T-lymphocyte fractions obtained from 24 females; 13 had essential thrombocythaemia (ET), eight polycythaemia vera (PV) and three myelofibrosis with myeloid metaplasia (MMM). All 24 of these patients had monoclonal patterns of X-inactivation in the granulocyte fraction. For the T-lymphocyte fraction, non-clonal patterns of X-inactivation were observed in 8/13 patients with ET, 7/8 with PV and 1/3 with MMM, while the remaining eight subjects were found to have monoclonal patterns of X-inactivation. Our findings suggest that the majority of the CMPD in these patients originated from a relatively committed progenitor cell without the capacity to differentiate into T cells, and convincingly demonstrated heterogeneity of lineage involvement.
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PMID:Clonality in chronic myeloproliferative disorders defined by X-chromosome linked probes: demonstration of heterogeneity in lineage involvement. 798 39

Inactive-X-chromosome genes in mammalian females have methylated CpG islands. We have questioned whether there are variable levels of cytosine methylation at different CpG sites within the island that might indicate the presence of primary sites of methylation which may be critical for the maintenance of gene repression and candidate sites for the initiation of inactivation. To address these questions, we have analyzed the methylation patterns of 32 CpG sites of the X-linked hypoxanthine phosphoribosyltransferase (Hprt) gene on the active and inactive X chromosomes of mouse tissues and cell lines, using genomic sequencing of bisulfite-treated genomic DNA. Cytosine is deaminated by bisulfite, but methylcytosine is not affected. Cell lines that were heterozygous for the Hprt deletion mutation (Hprtb-m3) and a functional Hprt allele were selected with 6-thioguanine. The resulting cell populations uniformly carry the intact Hprt allele on the inactive X chromosome. The methylation of these CpG sites was determined either by the direct sequence analysis of bisulfite-treated and amplified DNA or by the sequence analysis of clones derived from the amplified DNA. No CpG methylation was detected on the active Hprt genes from either males or the active X chromosome of females. On average, 22 CpGs were methylated in the other 50% of female DNA, and the level of methylation at individual sites varied from 42 to 100%. Analysis of the inactive Hprt gene in two cell lines showed that averages of 14 and 18 CpGs were methylated and that the frequency of methylation at 32 individual sites ranged from 3 to 100%. The highest frequency of methylation in cell lines coincided with the sequences flanking transcription initiation sites. These results suggest that methylation patterns are heterogeneous within a tissue and even in clonal cell populations and that specific subsets of CpG sites sustain high methylation frequencies which may be critical for the maintenance of X-chromosome inactivation. The bisulfite method identified which CpG sites were methylated on the inactive X chromosome, and it provided a quantitative estimate of the frequency of methylation of these sites in genomic DNA.
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PMID:CpG island promoter region methylation patterns of the inactive-X-chromosome hypoxanthine phosphoribosyltransferase (Hprt) gene. 796 37

Aplastic anaemia (AA) can be associated with disorders that are known to exhibit clonal haematopoiesis, like paroxysmal nocturnal haemoglobinuria (PNH), myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). It appears that the long term survivors of severe AA treated with immunosuppressive agents such as ATG have a continuing, late mortality caused by the evolution of clonal disorders which are not usually seen when bone marrow transplant is used. In children, typical AA may precede the onset of acute lymphoblastic leukemia (ALL). The aplastic phase is often transient and remission may be spontaneous or rapidly induced by steroid, and followed a few months later by acute leukaemia. This modality of presentation may be observed in up to 2-3% of all cases of paediatric ALL. A 13-year old girl who presented with two spontaneously reversible episodes of marrow aplasia has been reported recently. She developed ALL 8 months later. Southern analysis showed identical clonal immunoglobulin heavy chain gene rearrangement bands in her leukaemic cells as well as the marrow cells obtained at the two aplastic episodes. Hypoxanthine phosphoribosyltransferase polymorphism studies showed that all the ALL blast cells, bone marrow and peripheral cells during the two aplastic episodes all exhibited clonal haematopoiesis with the same X-chromosome inactivated. This case provides strong evidence that AA and ALL can represent evolution of the same abnormal clone.
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PMID:Childhood acute lymphoblastic leukaemia and aplastic anaemia. 806 86

The basis of a previously observed difference in the level of contribution of hypoxanthine phosphoribosyltransferase-deficient cells between the haematopoietic and non-haematopoietic tissues of chimaeric and heterozygous mice has been clarified by studying two populations of female mice that differ only in that one is heterozygous for a null allele at the hprt locus and the other is wild type at this locus. Both populations are heterozygous for an electrophoretic variant allele at the X-linked Pgk-1 locus, so that X-chromosome inactivation generates cells expressing different isozymes of phosphoglycerate kinase which can be assayed to monitor cell selection. The results show that hypoxanthine phosphoribosyltransferase deficiency itself, rather than an effect of another X-linked gene, causes a reduced level of contribution to haematopoietic tissues. Further, the extent of the depletion increases significantly with age, and this effect is due to a progressive reduction in the level of contribution to haematopoietic tissues rather than to an increase in the level of contribution to non-haematopoietic tissues.
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PMID:Age-dependent selection against hypoxanthine phosphoribosyl transferase-deficient cells in mouse haematopoiesis. 807 22

The goal of this study was to determine the developmental pattern of expression of the X-linked gene for hypoxanthine phosphoribosyltransferase (Hprt) during spermatogenesis and the relevance of this expression to X-chromosome inactivation during meiotic prophase. The results demonstrated that HPRT activity is maintained in mouse spermatogenic cells throughout development in spite of X-chromosome inactivation; however, specific activities of HPRT in meiotic and postmeiotic germ cells were significantly lower than in premeiotic ones. Maintenance of Hprt transcripts at all stages was also demonstrated. Interestingly, the highest level of Hprt transcripts was found in leptotene/zygotene spermatocytes, suggesting a hyperactivation of the Hprt gene and/or stabilization of Hprt transcripts in these cells. Hprt transcripts were present at very low levels in pachytene spermatocytes, and at slightly elevated levels in round spermatids. It was also found that the relative abundance of Hprt transcripts in the somatic cells of germ-cell-deficient testes was much greater than that in meiotic and postmeiotic germ cells, even though their activities of HPRT were similar. Examination of the translational status of Hprt transcripts in testicular cells revealed that while most of the transcript was translationally active in somatic cells of testes, less than half of the transcript was on polysomes in pachytene spermatocytes and round spermatids. Since no functional autosomal Hprt gene exists in the mouse, these data suggest that the germ cell maintains both transcript and protein product of the Hprt gene in spite of apparent X-chromosome inactivation.
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PMID:Expression of the Hprt gene during spermatogenesis: implications for sex-chromosome inactivation. 821 41


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