The Experts below are selected from a list of 186 Experts worldwide ranked by ideXlab platform

David W. Melton - One of the best experts on this subject based on the ideXlab platform.

  • production of a model for Lesch Nyhan Syndrome in hypoxanthine phosphoribosyltransferase deficient mice
    Nature Genetics, 1993
    Co-Authors: David W. Melton
    Abstract:

    The inherited disease Lesch-Nyhan Syndrome, which is caused by a deficiency of the enzyme hypoxanthine phosphoribosyltransferase (HPRT), is characterized by behavioural alterations, including self-injurious behaviour and mental retardation. Although HPRT-deficient mice have been generated using the embryonic stem cell system, no spontaneous behavioural abnormalities had been reported. We examined whether mice were more tolerant of HPRT deficiency because they were more reliant on adenine phosphoribosyltransferase (APRT) than HPRT for their purine salvage. The administration of an APRT inhibitor to HPRT-deficient mice induced persistent self-injurious behaviour. This combined genetic and biochemical model will facilitate the study of Lesch-Nyhan Syndrome and the evaluation of novel therapies.

  • Production of a model for Lesch–Nyhan Syndrome in hypoxanthine phosphoribosyltransferase–deficient mice
    Nature genetics, 1993
    Co-Authors: David W. Melton
    Abstract:

    The inherited disease Lesch-Nyhan Syndrome, which is caused by a deficiency of the enzyme hypoxanthine phosphoribosyltransferase (HPRT), is characterized by behavioural alterations, including self-injurious behaviour and mental retardation. Although HPRT-deficient mice have been generated using the embryonic stem cell system, no spontaneous behavioural abnormalities had been reported. We examined whether mice were more tolerant of HPRT deficiency because they were more reliant on adenine phosphoribosyltransferase (APRT) than HPRT for their purine salvage. The administration of an APRT inhibitor to HPRT-deficient mice induced persistent self-injurious behaviour. This combined genetic and biochemical model will facilitate the study of Lesch-Nyhan Syndrome and the evaluation of novel therapies.

C T Caskey - One of the best experts on this subject based on the ideXlab platform.

  • Lesch Nyhan Syndrome carrier and prenatal diagnosis
    Prenatal Diagnosis, 1995
    Co-Authors: R L Alford, J B Redman, W E Obrien, C T Caskey
    Abstract:

    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.

I. Willers - One of the best experts on this subject based on the ideXlab platform.

  • Germline mosaicism complicates molecular diagnosis of Lesch–Nyhan Syndrome
    Prenatal Diagnosis, 2004
    Co-Authors: I. Willers
    Abstract:

    A healthy female with a brother suffering from Lesch–Nyhan Syndrome was assigned a carrier status on the basis of haplotype analysis employing flanking and intragenic polymorphic markers of the HPRT gene. Her mother has been confirmed as a definite carrier by cell growth selection studies in cultured fibroblasts. In our proposita's first pregnancy, a male fetus was identified carrying the risk allele. Afterwards, the underlying novel mutation A161E (GCAGAA at position c482) could be identified in the affected brother and in the heterozygous mother but not in the DNA of the pregnant sister and fetus. The fetus was also confirmed to be normal by uptake of 14C-hypoxanthine in cultured amniotic cells. To test the discrepancy, the investigation was extended by recruiting additional family members. The data obtained showed that the mother had passed her risk haplotype to the affected son as well as to her mutation-carrying and non–mutation-carrying daughters. This provides the first evidence of concomitant somatic and germline mosaicism in Lesch–Nyhan Syndrome. The study has a bearing on genetic counselling and cautions against the reliability of only using indirect genetic diagnosis even with intragenic markers. Copyright © 2004 John Wiley & Sons, Ltd.

  • germline mosaicism complicates molecular diagnosis of Lesch Nyhan Syndrome
    Prenatal Diagnosis, 2004
    Co-Authors: I. Willers
    Abstract:

    A healthy female with a brother suffering from Lesch–Nyhan Syndrome was assigned a carrier status on the basis of haplotype analysis employing flanking and intragenic polymorphic markers of the HPRT gene. Her mother has been confirmed as a definite carrier by cell growth selection studies in cultured fibroblasts. In our proposita's first pregnancy, a male fetus was identified carrying the risk allele. Afterwards, the underlying novel mutation A161E (GCAGAA at position c482) could be identified in the affected brother and in the heterozygous mother but not in the DNA of the pregnant sister and fetus. The fetus was also confirmed to be normal by uptake of 14C-hypoxanthine in cultured amniotic cells. To test the discrepancy, the investigation was extended by recruiting additional family members. The data obtained showed that the mother had passed her risk haplotype to the affected son as well as to her mutation-carrying and non–mutation-carrying daughters. This provides the first evidence of concomitant somatic and germline mosaicism in Lesch–Nyhan Syndrome. The study has a bearing on genetic counselling and cautions against the reliability of only using indirect genetic diagnosis even with intragenic markers. Copyright © 2004 John Wiley & Sons, Ltd.

Joseph G Barone - One of the best experts on this subject based on the ideXlab platform.

  • Lesch Nyhan Syndrome presenting as acute renal failure secondary to obstructive uropathy
    Urology, 2000
    Co-Authors: Muralikk Ankem, David B Glazier, Joseph G Barone
    Abstract:

    Lesch-Nyhan Syndrome is a rare genetic disorder characterized by mental retardation, self-mutilation, choreoathetosis, and hyperuricemia. The disease is caused by a mutation in the hypoxanthine-guanine phosphoribosyltransferase gene and is transmitted as a sex-linked recessive disorder. Since hyperuricemia is the primary metabolic problem caused by a hypoxanthine-guanine phosphoribosyltransferase mutation, urologic evaluation and treatment is often necessary for children with this disease. We report a 3-year-old boy who presented with anuric renal failure secondary to bilateral obstructing uric acid calculi. The evaluation of T lymphocytes revealed a hypoxanthine-guanine phosphoribosyltransferase mutation consistent with Lesch-Nyhan Syndrome. The diagnosis and urologic management of this disorder is discussed.

Josef Hyánek - One of the best experts on this subject based on the ideXlab platform.

  • Urinary pterins in Lesch-Nyhan Syndrome.
    Advances in experimental medicine and biology, 1991
    Co-Authors: Ivan Sebesta, Jakub Krijt, Stanislav Kmoch, Josef Hyánek
    Abstract:

    The Lesch-Nyhan Syndrome results from a complete deficiency of the purine salvage enzyme hypoxanthine guanine phosphoribosyltransferase (HPRT E.C.2.4.2.8). Clinical manifestations include muscle hypotonia, torsion dystonia, delayed motor development, compulsive self-mutilative behaviour, and mental handicap, as well as increased quantities of uric acid in body fluids, which may lead to nephropathy, renal calculi, tophi and gouty arthritis. The latter manifestations are effectively controlled using allopurinol and the pathophysiological mechanism of overproduction of uric acid is known. However, there is no effective treatment for the neurologic and behavioural features and the processes by which a lack of HPRT brings about the neurological dysfunction remain unclear (1).