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1.
Science ; 166(3912): 1533-5, 1969 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-17695080

RESUMO

The urate pool and daily turnover of urate, together with the rate of incorporation of glycine into urate, were measured in three asymptomatic mothers who had sons with various degrees of deficiency of hypoxanthine-guanine phosphoribosyltransferase activity. Two of these mothers had abnormally increased values for the urate pool, urate turnover, and 24-hour urinary excretion of uric acid. These two mothers also had reduced hypoxanthine-guanine phosphoribosyltransferase activity and increased adenine phosphoribosyltransferase activity in erythrocyte lysates. All three mothers showed an abnormal increase in urate production, as judged by the rate of incorporation of glycinie into urate.


Assuntos
Heterozigoto , Hipoxantina Fosforribosiltransferase/deficiência , Síndrome de Lesch-Nyhan/genética , Ácido Úrico/metabolismo , Adenina Fosforribosiltransferase/sangue , Adolescente , Adulto , Creatinina/urina , Eritrócitos/enzimologia , Feminino , Glicina/metabolismo , Humanos , Hipoxantina Fosforribosiltransferase/sangue , Hipoxantina Fosforribosiltransferase/metabolismo , Síndrome de Lesch-Nyhan/metabolismo , Masculino , Mães , Ácido Úrico/sangue , Ácido Úrico/urina
2.
Biochim Biophys Acta ; 927(1): 1-7, 1987 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-3098299

RESUMO

Two human lymphoblastic cell lines, deficient in methylthioadenosine phosphorylase (MTAP) activity, were found to have increased rates of de novo purine synthesis. These MTAP- cell lines were K562, an undifferentiated leukemic line and CCRF-CEM, a leukemic line of T-cell origin. Another T-cell line, CCRF-HSB-2 was found to be deficient in activity. However, this line did not demonstrate elevated rates of purine synthesis. Purine metabolism in the above cell cultures was compared with MTAP+ human B-cell lines and two human T-cell lines (MOLT-3 and MOLT-4). In all the MTAP+ cell lines, the rate of de novo purine synthesis was inhibited by the presence of methylthioadenosine in the assay medium (10 microM concentration produced more than 90% inhibition). However, purine synthesis in the MTAP- cells was resistant to inhibition by methylthioadenosine. Adenine in the assay medium inhibited de novo purine synthesis in MTAP+ and MTAP- cells to a similar degree. This inhibition was dose dependent and was elicited by concentrations similar to those of methylthioadenosine. Growth of the cell lines in culture was not affected by either methylthioadenosine or adenine at the concentrations which produced inhibition of purine synthesis. These results suggest that purine synthesis in MTAP+ cells is inhibited by adenine formed from the phosphorolytic cleavage of methylthioadenosine by methylthioadenosine phosphorylase.


Assuntos
Desoxiadenosinas , Linfócitos/metabolismo , Pentosiltransferases/deficiência , Purina-Núcleosídeo Fosforilase/deficiência , Purinas/biossíntese , Adenina/farmacologia , Adenosina/análogos & derivados , Adenosina/farmacologia , Linfócitos B/metabolismo , Linhagem Celular , Humanos , Cinética , Leucemia Linfoide/metabolismo , Linfócitos/efeitos dos fármacos , Linfócitos T/metabolismo , Tionucleosídeos/farmacologia
3.
Biochim Biophys Acta ; 1096(2): 95-100, 1991 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-1705826

RESUMO

Human erythrocyte hypoxanthine-guanine phosphoribosyltransferase (HPRT) is inactivated by iodoacetate in the absence, but not in the presence, of the substrate, 5-phospho-alpha-D-ribosyl-1-pyrophosphate (PRib-PP). Treatment of HPRT with [14C]iodoacetate followed by tryptic digestion, peptide separation and sequencing has shown that Cys-22 reacts with iodoacetate only in the absence of PRib-PP; this strongly suggests that Cys-22 is in or near the PRib-PP binding site. In contrast, Cys-105 reacts with [14C]iodoacetate both in the presence and absence of PRib-PP. Carboxymethylation of Cys-22 resulted in an increase in the Km for PRib-PP, but no change in Vmax. Storage of HPRT also resulted in an increase in the Km for PRib-PP and a decrease in its susceptibility to inactivation by iodoacetate. Dialysis of stored enzyme against 1 mM dithiothreitol resulted in a marked decrease in Km for PRib-PP. The stoichiometry of the reaction of [14C]iodoacetate with Cys-22 in HPRT leading to inactivation (approx. 1 residue modified per tetramer) showed that, in this preparation of HPRT purified from erythrocytes, only about 25% of the Cys-22 side chains were present as free and accessible thiols. Titration of thiol groups [with 5,5'-dithiobis(2-nitrobenzoic acid)] and the effect of dithiothreitol on Km for PRib-PP indicate that oxidation of thiol groups occurs on storage of HPRT, even in the presence of 1 mM beta-mercaptoethanol.


Assuntos
Hipoxantina Fosforribosiltransferase/metabolismo , Fosforribosil Pirofosfato/metabolismo , Sítios de Ligação , Cromatografia Líquida de Alta Pressão , Ácido Ditionitrobenzoico/química , Eritrócitos/enzimologia , Humanos , Hipoxantina Fosforribosiltransferase/antagonistas & inibidores , Hipoxantina Fosforribosiltransferase/química , Técnicas In Vitro , Iodoacetatos/farmacologia , Ácido Iodoacético , Fragmentos de Peptídeos/química
4.
Biochim Biophys Acta ; 562(1): 162-76, 1979 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-435498

RESUMO

Procedures for assaying the rate of purine de novo synthesis in cultured fibroblast cells have been compared. These were (i) the incorporation of [(14)C]-glycine or [(14)C]formate in alpha-N-formylglycinamide ribonucleotide (an intermediate in the purine synthetic pathway) and (ii) the incorporation of [(14)C]-formate into newly synthesised cellular purines and purines excreted by the cell into the medium. Fibroblast cells, derived from patients with a deficiency of hypoxanthine phosphoribosyltransferase (HPRT-) (EC 2.4.2.8) and increased rates of purine de novo synthesis, were compared with fibroblasts from healthy subjects (HPRT+). Fetal calf serum, which was used to supplement the assay and cell growth medium, was found to contain sufficient quantities of the purine base hypoxanthine to inhibit purine de novo synthesis in HPRT+ cells. This inhibition was the basis of differentiation between HPRT- and HPRT+ cells. In the absence of added purine base, both cell types had similar capacities for purine de novo synthesis. This result contrasts with the increased rates of purine de novo synthesis reported for a number of human HPRT- cells in culture but conforms recent studies made on human HPRT- lymphoblast cells. The intracellular concentration and utilisation of 5-phosphoribosyl-1-pyrophosphate (P-Rib-PP), a substrate and potential controlling factor for purine de novo synthesis, were determined in HPRT- and HPRT+ cells. The rate of utilisation of P-Rib-PP in the salvage of free purine bases was far greater than that in purine de novo synthesis. Although HPRT- cells had a 3-fold increase in P-Rib-PP content, the rate of P-Rib-PP generation was similar to HPRT+ cells. Thus, in fibroblasts, the concentration of P-Rib-PP appears to be critical in the control of de novo purine synthesis and its preferential utilisation in the HPRT reaction limits its availability for purine de novo synthesis. In vivo, HPRT+ cells, in contrast to HPRT- cells, may be operating purine de novo synthesis at a reduced rate because of their ability to reutilise hypoxanthine.


Assuntos
Pentosefosfatos/metabolismo , Fosforribosil Pirofosfato/metabolismo , Purinas/biossíntese , Adenina/farmacologia , Sangue , Células Cultivadas , Formiatos/metabolismo , Glicina/metabolismo , Humanos , Hipoxantina Fosforribosiltransferase/deficiência , Hipoxantina Fosforribosiltransferase/metabolismo , Hipoxantinas/farmacologia
5.
Biochim Biophys Acta ; 1087(2): 205-11, 1990 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-2223882

RESUMO

A plasmid, pRG1, has been constructed by incorporating the coding sequence of human hypoxanthine-guanine phosphoribosyltransferase (HPRT) into the expression vector pT7-7. Expression of human HPRT has been achieved in HPRT- Escherichia coli cells transformed with pRG1 and pGP1-2, as shown by: (1) exclusive labelling with [35S]methionine of a polypeptide with the same mobility as purified human HPRT on SDS-PAGE; and (2) measurement of HPRT activity after cell lysis. Although the majority of the recombinant HPRT was present in the particulate fraction after cell lysis and centrifugation, sufficient HPRT activity was present in the supernatant fraction to allow comparison with the HPRT purified from human erythrocytes and the activity in human haemolysates and lymphoblast lysates. Small differences in electrophoretic mobility on native gels were found between HPRT activity from these sources. The Km values of recombinant HPRT for the substrates 5-phospho-alpha-D-ribosyl-1-pyrophosphate and guanine were compared with those of lymphoblast and erythrocyte HPRT.


Assuntos
Escherichia coli/genética , Expressão Gênica , Hipoxantina Fosforribosiltransferase/genética , Cromatografia em Gel , Clonagem Molecular , DNA/genética , Eletroforese em Gel de Poliacrilamida , Éxons , Genes , Humanos , Hipoxantina Fosforribosiltransferase/química , Hipoxantina Fosforribosiltransferase/metabolismo , Cinética , Metionina/farmacologia , Plasmídeos , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transformação Bacteriana
6.
Eur J Hum Genet ; 5(1): 15-21, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9156316

RESUMO

Homocystinuria, due to a deficiency of the enzyme cystathionine beta-synthase (CBS), is an inborn error of sulphur-amino acid metabolism. This is an autosomal recessive disease which results in hyperhomocysteinaemia and a wide range of clinical features, including optic lens dislocation, mental retardation, skeletal abnormalities and premature thrombotic events. We report the identification of 5 missense mutations in the protein-coding region of the CBS gene from 3 patients with pyridoxine-nonresponsive homocystinuria. Reverse-transcription PCR was used to amplify CBS cDNA from each patient and the coding region was analysed by direct sequencing. The mutations detected included 3 novel (1058C-->T, 992C-->A and 1316G-->A) and 2 previously identified (430G-->A and 833C-->T) base alterations in the CBS cDNA. Each of these mutations predicts a single amino acid substitution in the CBS polypeptide. Appropriate cassettes of patient CBS cDNA, containing each of the above defined mutations, were used to replace the corresponding cassettes of normal CBS cDNA sequence within the bacterial expression vector pT7-7. These recombinant mutant and normal CBS constructs were expressed in Escherichia coli cells and the catalytic activities of the mutant proteins were compared with normal. All of the mutant proteins exhibited decreased catalytic activity in vitro, which confirmed the association between the individual mutation and CBS dysfunction in each patient.


Assuntos
Cistationina beta-Sintase/genética , Homocistinúria/genética , Mutação , Adolescente , Western Blotting , Criança , Cistationina beta-Sintase/deficiência , Análise Mutacional de DNA , Feminino , Homocisteína/análise , Homocistinúria/fisiopatologia , Homocistinúria/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Reação em Cadeia da Polimerase , Piridoxina/uso terapêutico , Mapeamento por Restrição
7.
Clin Pharmacol Ther ; 28(1): 45-51, 1980 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7389253

RESUMO

The response to indacrinone, a new indanone diuretic, was studied in 12 healthy subjects. Ten milligrams alone and in combination with either 2.5 mg or 5 mg amiloride was given in a randomized double-blind study with placebo control to study its action and to assess the optimum combination. Indacrinone alone induced an increase in urine flow rate and in sodium, potassium, and hydrogen ion excretion for at least 8 hr. Indacrinone also induced an initial uricosuria in the first 4 hr, followed by urate retention in the subsequent 12 to 24 hr, with no resultant change in the mean 24-hr urate excretion and minimal changes in the serum urate concentrations. The addition of 2.5 mg amiloride to the 10 mg indacrinone lowered potassium excretion to control levels, whereas addition of 5 mg amiloride resulted in net retention of potassium. With both doses of amiloride, the increased free hydrogen ion excretion after indacrinone returned to placebo levels. There were minor increases in serum creatinine, consistent with volume depletion due to the diuresis. There was a reduction in urinary calcium excretion. Our study shows that the combination of 10 mg indacrinone and 2.5 mg amiloride induces useful diuresis with minimal overall effect on urate, potassium, and hydrogen ion excretion.


Assuntos
Amilorida/farmacologia , Diuréticos/farmacologia , Indanos/farmacologia , Indenos/farmacologia , Potássio/urina , Pirazinas/farmacologia , Uricosúricos/farmacologia , Adulto , Cálcio/urina , Cloretos/urina , Creatinina/sangue , Método Duplo-Cego , Sinergismo Farmacológico , Eletrólitos/urina , Humanos , Indanos/efeitos adversos , Masculino , Fosfatos/urina , Sódio/urina
8.
Gene ; 108(2): 299-304, 1991 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-1840549

RESUMO

A complete deficiency of the purine salvage enzyme, hypoxanthine phosphoribosyltransferase (HPRT; EC 2.4.2.8), in man results in the Lesch-Nyhan (LN) syndrome. Two unrelated patients with the full LN syndrome showed no evidence of a major alteration to the gene encoding HPRT (HPRT) by restriction endonuclease analysis, but exhibited negligible levels of HPRT mRNA on Northern blots. DNA from these patients was characterised further. Amplification, by the polymerase chain reaction (PCR), of individual HPRT-exon fragments from genomic DNA followed by nucleotide (nt) sequence analysis using automated technology, revealed single-base mutations in each patient. One patient has an insertion of a T within exon-2, which places a stop codon in frame, presumably resulting in premature termination of translation of the HPRT mRNA. The other patient has a G----A base substitution at the 5' end of intron-6, at the junction of exon-6 and intron-6. Although dot blot analysis indicated negligible HPRT mRNA in lymphoblast cells from both patients, we were successful in amplifying HPRT cDNA using PCR. Direct nt sequence analysis of the amplified cDNA confirmed the insertion of a T in exon-2 in the one patient and revealed a complete deletion of exon-6 in the other patient, the latter event presumably arising due to aberrant splicing of primary message. Both mutations were also confirmed by hybridisation of amplified genomic DNA with allele-specific oligodeoxyribonucleotide probes. This study illustrates two approaches for analysing DNA mutations at the molecular level and demonstrates the power of PCR technology in the study of genetic diseases.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Hipoxantina Fosforribosiltransferase/genética , Síndrome de Lesch-Nyhan/genética , Sequência de Bases , Northern Blotting , Códon/genética , Éxons/genética , Feminino , Humanos , Hipoxantina Fosforribosiltransferase/deficiência , Síndrome de Lesch-Nyhan/enzimologia , Dados de Sequência Molecular , Mutação/genética , Reação em Cadeia da Polimerase , Biossíntese de Proteínas/genética
9.
Mol Biochem Parasitol ; 98(1): 29-41, 1999 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-10029307

RESUMO

The human malaria parasite Plasmodium falciparum is auxotrophic for purines and relies on the purine salvage pathway for the synthesis of its purine nucleotides. Hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) is a key purine salvage enzyme in P. falciparum, making it a potential target for chemotherapy. Previous attempts to purify this enzyme have been unsuccessful because of the difficulty in obtaining cultured parasite material and because of the inherent instability of the enzyme during purification and storage. Other groups have tried to express recombinant P. falciparum HGXPRT but only small amounts of activity were obtained. The successful expression of recombinant P. falciparum HGXPRT in Escherichia coli has now been achieved and the enzyme purified to homogeneity in mg quantities. The measured molecular mass of 26 229+/-2 Da is in excellent agreement with the calculated value of 26232 Da. A method to stabilise the activity and to reactivate inactive samples has been developed. The subunit structure of P. Jilciparum HGXPRT has been determined by ultracentrifugation in the absence (tetramer) and presence (dimer) of KC1. Kinetic constants were determined for 5-phospho-alpha-D-ribosyl-1-pyrophosphate, for the three naturally-occurring 6-oxopurine bases guanine, hypoxanthine, and xanthine and for the base analogue, allopurinol. Differences in specificity between the purified P. falciparum HGXPRT and human hypoxanthine guanine phosphoribosyltransferase enzymes were detected which may be able to be exploited in rational drug design.


Assuntos
Hipoxantina Fosforribosiltransferase/metabolismo , Pentosiltransferases/metabolismo , Plasmodium falciparum/enzimologia , Animais , Ativação Enzimática , Estabilidade Enzimática , Humanos , Hipoxantina Fosforribosiltransferase/antagonistas & inibidores , Hipoxantina Fosforribosiltransferase/genética , Hipoxantina Fosforribosiltransferase/isolamento & purificação , Espectrometria de Massas , Cloreto de Mercúrio/farmacologia , Peso Molecular , Pentosiltransferases/antagonistas & inibidores , Pentosiltransferases/genética , Pentosiltransferases/isolamento & purificação , Cloreto de Potássio/farmacologia , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Especificidade da Espécie , Especificidade por Substrato
10.
Biochem Pharmacol ; 33(12): 1929-32, 1984 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-6732850

RESUMO

Glutathione transferases are believed to play an important protective role in the various tissues of animals and man by catalysing the glutathione conjugation of electrophilic drugs and electrophilic drug metabolites. Many of these compounds have the potential to react with vital cellular macromolecules in the absence of this enzyme system. We have investigated the interaction of a number of high ceiling diuretics with the glutathione transferases contained in the cytosolic fraction of the rat liver. Of bumetanide, ethacrynic acid, furosemide, indacrynic acid and tienilic acid, only ethacrynic acid was conjugated with glutathione. Further experiments revealed that ethacrynic, indacrynic and tienilic acids are all potent inhibitors of glutathione S- aryltransferase . Glutathione S- alkyltransferase and glutathione S-epoxide transferase were also inhibited by the diuretics, but to a lesser extent than glutathione S- aryltransferase . The diuretics giving the greatest inhibition of these reactions were chemically related to ethacrynic acid. The concept where inhibition of glutathione-S-transferase by a drug may enhance its own toxicity is considered. This mechanism has also the potential of enhancing the toxicity of other concurrently administered drugs which normally require glutathione S-transferase for detoxication.


Assuntos
Diuréticos/toxicidade , Glutationa Transferase/antagonistas & inibidores , Animais , Ácido Etacrínico/toxicidade , Fígado/efeitos dos fármacos , Masculino , Ratos , Ratos Endogâmicos , Solubilidade , Relação Estrutura-Atividade , Ticrinafeno/toxicidade
11.
Biochem Pharmacol ; 34(12): 2157-61, 1985 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-4004933

RESUMO

Seven soluble rat liver glutathione S-transferase isozymes were isolated and the inhibition of these isozymes by selected diuretics was investigated using 1-chloro-2,4-dinitrobenzene as substrate. All isozymes were inhibited to some extent under the experimental conditions used, but there was significant isozyme dependent selectivity of inhibition. The greatest inhibitory effect (over 80%) was found when the phenoxyacetic acid diuretics and indacrynic acid were incubated with glutathione S-transferase 3-3, 3-4 and 4-4. The sulphamoylbenzoic acid diuretics, furosemide and bumetanide, were found to have a lesser effect on the isozymes studies. As glutathione S-transferase are thought to play an important protective role in the various tissues of animals and man, by catalysing the glutathione conjugation of electrophilic drugs and drug metabolites, their inhibition may be toxicologically important.


Assuntos
Diuréticos/toxicidade , Glutationa Transferase/antagonistas & inibidores , Isoenzimas/antagonistas & inibidores , Fígado/enzimologia , Animais , Diuréticos/metabolismo , Fígado/efeitos dos fármacos , Masculino , Ratos , Ratos Endogâmicos
12.
Clin Chim Acta ; 71(2): 303-8, 1976 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-183920

RESUMO

Urate production and excretion were studied in heterozygous parents of a child with glucose-6-phosphatase deficiency. Both parents demonstrated glucose-6-phosphatase concentrations in platelets intermediate between those in the homozygote and the normal. The miscible urate pool and turnover rate, the rate of incorporation of [14C]glycine into urate, the renal clearance of urate and the percentage excretion of labelled urate by the renal route were within the normal range in both heterozygotes, as were the serum cholesterol and triglyceride concentrations. Thus, a partial deficiency of glucose-6-phosphatase was not associated with the abnormalities of urate or lipoprotein metabolism which are features of homozygous glucose-6-phosphatase deficiency. Erythrocyte phosphoribosyl-pyrophosphate concentration, an increased concentration of which has been postulated as the mechanism responsible for the increased de novo purine biosynthesis in glucose-6-phosphatase deficiency, was found to be within the normal range in erythrocytes from both a homozygote and a heterozygote for this condition.


Assuntos
Doença de Depósito de Glicogênio Tipo I/sangue , Ácido Úrico/metabolismo , Adulto , Plaquetas/enzimologia , Pré-Escolar , Eritrócitos/metabolismo , Feminino , Glucose-6-Fosfatase/metabolismo , Glucofosfatos/metabolismo , Glicina/metabolismo , Heterozigoto , Humanos , Masculino , Fosforribosil Pirofosfato/sangue
13.
Clin Chim Acta ; 80(1): 203-7, 1977 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-908142

RESUMO

A simple spectrophotometric assay is described based on the conversion of hypoxanthine to inosine monophosphate and precipitation of both the reaction product and protein with lanthanum phosphate. The extent of conversion is determined by the fall in absorbance of hypoxanthine at 249 nm. The assay is suitable for screening red cell lysates for hypoxanthine-guanine phosphoribosyltransferase deficiency.


Assuntos
Hipoxantina Fosforribosiltransferase/sangue , Eritrócitos/enzimologia , Humanos , Síndrome de Lesch-Nyhan/enzimologia , Métodos , Espectrofotometria Ultravioleta , Fatores de Tempo
14.
Clin Chim Acta ; 163(3): 301-8, 1987 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-3581473

RESUMO

A simple and rapid spectrophotometric assay for the estimation of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity in human tissues is described. It is based on the increase in absorbance at 257.5 nm which occurs when the substrate guanine is converted to its 5'-mononucleotide, GMP. The assay has been developed to measure HGPRT activity in erythrocyte and lymphocyte lysates and in brain homogenates, and has been used in the screening of patients with hyperuricaemia and/or hyperuricosuria for HGPRT deficiency. It has also been used to determine the steady-state kinetic constants of a mutant form of the enzyme. The spectrophotometric assay is compared with the radioactive assay currently used to measure HGPRT activity.


Assuntos
Encéfalo/enzimologia , Guanina/metabolismo , Hipoxantina Fosforribosiltransferase/metabolismo , Idoso , Eritrócitos/enzimologia , Feminino , Humanos , Hipoxantina Fosforribosiltransferase/deficiência , Hipoxantina Fosforribosiltransferase/genética , Cinética , Linfócitos/enzimologia , Masculino , Mutação , Espectrofotometria
15.
Clin Nephrol ; 18(1): 1-8, 1982 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7116701

RESUMO

A large family with medullary cystic disease is described to show that juvenile nephronophthisis and medullary cystic disease should not be differentiated by age of onset and type of inheritance. The age at diagnosis of six family members with medullary cystic disease ranged from 4-32 years, and age at death from renal failure or commencement of dialysis from 7-48 years. A mother of two children with renal failure in early childhood has histological evidence of medullary cystic disease with normal renal function. We suggest that juvenile nephronophthisis and medullary cystic disease are the same conditions and that the disease be classified as medullary cystic disease, autosomal dominant or recessive form. When undertaking genetic counselling in the parents of children with medullary cystic disease, we suggest that renal biopsy may need to be considered even if their renal function is normal. Three patients presented with gout, and the possibility of an association with medullary cystic disease should be considered when more than one member of a family develops gout. Two patients died of status epilepticus, and epilepsy is probably an added association of medullary cystic disease.


Assuntos
Nefropatias/genética , Rim/patologia , Adolescente , Adulto , Autopsia , Criança , Pré-Escolar , Feminino , Gota/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Estado Epiléptico/patologia
16.
Adv Exp Med Biol ; 253A: 151-4, 1989.
Artigo em Inglês | MEDLINE | ID: mdl-2576180

RESUMO

1. Immunological quantitation of the HPRT proteins, together with DNA and RNA studies have defined further the heterogeneous nature of HPRT-deficiency in our patients. 2. These studies have dictated possible approaches for further characterisation of the HPRT enzyme in our patients. In the two Lesch-Nyhan patients, both the protein and the usual cDNA approach would appear difficult. 3. A BamHI polymorphism has been detected in Patient A. 4. Sequence data confirmed the creation of this BamHI site by a single C----T transition at position 602 in the coding sequence. 5. Sequencing of other patients is proceeding and use is being made of the Polymerase Chain Reaction (PCR)10 for amplification of specific segments of HPRT coding sequence.


Assuntos
DNA/genética , Hipoxantina Fosforribosiltransferase/genética , RNA Mensageiro/genética , Linhagem Celular Transformada , Eritrócitos/enzimologia , Humanos , Hipoxantina Fosforribosiltransferase/sangue , Hipoxantina Fosforribosiltransferase/deficiência , Polimorfismo de Fragmento de Restrição
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