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Citations to this article

Molecular basis of hypoxanthine-guanine phosphoribosyltransferase deficiency in a patient with the Lesch-Nyhan syndrome.
J M Wilson, W N Kelley
J M Wilson, W N Kelley
Published May 1, 1983
Citation Information: J Clin Invest. 1983;71(5):1331-1335. https://doi.org/10.1172/JCI110884.
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Research Article

Molecular basis of hypoxanthine-guanine phosphoribosyltransferase deficiency in a patient with the Lesch-Nyhan syndrome.

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Abstract

We have investigated the molecular basis of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency in a patient who presented with the Lesch-Nyhan syndrome. A catalytically incompetent form of HPRT has been isolated from this patient's erythrocytes and lymphoblasts. This enzyme variant, which we have termed HPRTKinston, is indistinguishable from the normal enzyme in terms of its intracellular concentration and maximal velocity, but differs with respect to its isoelectric point (more basic) and Michaelis constants for both substrates (markedly elevated). The tryptic peptides of HPRTKinston were mapped by reverse-phase high pressure liquid chromatography in an attempt to define the precise abnormality in its primary structure. Sequence analysis of the single aberrant tryptic peptide in HPRTKinston revealed an aspartic acid to asparagine amino acid substitution at position 193. Electrophoretic analysis of the CNBr peptides of HPRTKinston confirmed the location of the proposed mutation. This amino acid substitution can be explained by a single nucleotide change in the codon for aspartic acid 193 (GAC leads to AAC). This is the first specific mutation described at the molecular level in a patient with the Lesch-Nyhan syndrome.

Authors

J M Wilson, W N Kelley

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Total citations by year

Year: 2017 2015 2009 2004 2003 2000 1995 1994 1993 1992 1991 1990 1989 1988 1987 1986 1985 1984 1983 1962 Total
Citations: 1 1 1 1 1 2 1 3 1 3 1 3 5 4 1 4 5 4 1 1 44
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Citations to this article (44)

Title and authors Publication Year
Unapparent hypoxanthine-guanine phosphoribosyltransferase deficiency
RJ Torres, S Puente, A Menendez, N Fernandez-Garcia
Clinica chimica acta; international journal of clinical chemistry 2017
Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease
R Schiffmann
Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease 2015
Genetic Diseases of the Kidney
K Ichida, M Hosoyamada, T Hosoya, H Endou
Genetic Diseases of the Kidney 2009
Neurocutaneous Disorders
ES Roach, VS Miller
Neurocutaneous Disorders 2004
A novel point mutation (I137T) in the conserved 5-phosphoribosyl-1-pyrophosphate binding motif of hypoxanthine-guanine phosphoribosyltransferase (HPRTJerusalem) in a variant of Lesch–Nyhan syndrome
E Zoref-Shani, Y Bromberg, J Hirsch, S Feinstein, Y Frishberg, O Sperling
Molecular Genetics and Metabolism 2003
The spectrum of inherited mutations causing HPRT deficiency: 75 new cases and a review of 196 previously reported cases
HA Jinnah, LD Gregorio, JC Harris, WL Nyhan, JP O’Neill
Mutation Research/Reviews in Mutation Research 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
E Zoref-Shani, S Feinstein, Y Frishberg, Y Bromberg, O Sperling
Biochimica et Biophysica Acta 2000
Southern analysis reveals a large deletion at the hypoxanthine phosphoribosyltransferase locus in a patient with Lesch-Nyhan syndrome
PJ Renwick, AJ Birley, CM McKeown, M Hultén
Clinical Genetics 1995
Analysis of in vivo mutation in exon 8 of the rat hprt gene
RA Mittelstaedt, RH Heflich
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 1994
Working paper no. 2 Spontaneous mutations in mammalian cells
BW Glickman, VA Saddi, J Curry
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 1994
Working paper no. 3 Somatic mutant frequency, mutation rates and mutational spectra in the human population in vivo
J Cole, TR Skopek
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 1994
H-2Dd exploits a four residue peptide binding motif
M Corr, LF Boyd, EA Padlan, DH Margulies
Journal of Experimental Medicine 1993
The gene encoding hypoxanthine-guanine phosphoribosyltransferase as target for mutational analysis: PCR cloning and sequencing of the cDNA from the rat
JG Jansen, H Vrieling, AA van Zeeland, GR Mohn
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 1992
Spectrum of spontaneously occurring mutations in the hprt gene of V79 Chinese hamster cells
LH Zhang, H Vrieling, AA van Zeeland, D Jenssen
Journal of Molecular Biology 1992
Clinical quiz
KE Meyers, PD Thomson, J Cartwright
Pediatric Nephrology 1992
Mutational analysis of the structure and function of the adenine phosphoribosyltransferase enzyme of Chinese hamster
JG de Boer, BW Glickman
Journal of Molecular Biology 1991
Molecular basis for the properties of the thyroxine-binding globulin-slow variant in American Blacks
MR Waltz, TN Pullman, K Takeda, P Sobieszczyk, S Refetoff
Journal of Endocrinological Investigation 1990
Hypoxanthine guanine phosphoribosyltransferase deficiency: nucleotide substitution causing Lesch-Nyhan syndrome identified for the first time among Japanese
S Fujimori, N Kamatani, Y Nishida, N Ogasawara, I Akaoka
Human Genetics 1990
Clinical quiz. Elevated urinary uric acid excretion (UUAE).
Schoeneman MJ
Pediatric nephrology (Berlin, Germany) 1990
Molecular basis of hypoxanthine-guanine phosphoribosyltransferase deficiency in ten subjects determined by direct sequencing of amplified transcripts
BL Davidson, SA Tarlé, TD Palella, WN Kelley
Journal of Clinical Investigation 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
FF Snyder, JE Joyce, T Carter-Edwards, R Joshi, HL Rylance, RC Wallace, G Nuki
Journal of Inherited Metabolic Disease 1989
Molecular Analysis of Hypoxanthine-Guanine Phosphoribosyltransferase Mutations in Five Unrelated Japanese Patients
T Igarashi, M Minami, Y Nishida
Pediatrics International 1989
Genetic and Therapeutic Aspects of Lipid and Purine Metabolism
G Wolfram
1989
Human Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency
BL Davidson, M Pashmforoush, WN Kelley, TD Palella
The Journal of biological chemistry 1989
Biochemical genetics of HPRTCapeTown: is the defect in the HPRT gene?
T Galloon, EH Harley
Journal of Inherited Metabolic Disease 1988
Analysis of cDNA encoding the hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) of Schistosoma mansoni; a putative target for chemotherapy
SP 3rd, JH McKerrow, GR Newport, CC Wang
Nucleic Acids Research 1988
Human hypoxanthine-guanine phosphoribosyltransferase: a single nucleotide substitution in cDNA clones isolated from a patient with Lesch-Nyhan syndrome (HPRTMidland)
BL Davidson, TD Palella, WN Kelley
Gene 1988
Review: Thalassemia: Molecular Pathology and Management
MH Steinberg
The American Journal of the Medical Sciences 1988
HB Mississippi [β44(CD3)SeråG]: A New Variant with Anomalous Properties
JG Adams, WT Morrison, RL Barlow, MH Steinberg
Hemoglobin 1987
A molecular survey of hypoxanthine-guanine phosphoribosyltransferase deficiency in man
JM Wilson, JT Stout, TD Palella, BL Davidson, WN Kelley, CT Caskey
Journal of Clinical Investigation 1986
Nucleotide sequence and deduced amino acid sequence of Escherichia coli adenine phosphoribosyl-transferase and comparison with other analogous enzymes
HV Hershey, MW Taylor
Gene 1986
Approaches to determining mutation rates in human DNA
J Delehanty, RL White, ML Mendelsohn
Mutation Research/Reviews in Genetic Toxicology 1986
Purine and Pyrimidine Metabolism in Man V
WL Nyhan, LF Thompson, RW Watts
1986
Molecular genetic approaches to neurologic and psychiatric diseases
MB Rosenberg, C Hansen, XO Breakefield
Progress in Neurobiology 1985
The biochemical basis of the behavioral disorder in the Lesch-Nyhan syndrome
AA Baumeister, GD Frye
Neuroscience & Biobehavioral Reviews 1985
Genetic and Metabolic Disease in Pediatrics
L Pinsky, M Kaufman
Genetic and Metabolic Disease in Pediatrics 1985
Immunology of Rheumatic Diseases
S Gupta, N Talal
1985
Common characteristics of mutant adenine phosphoribosyltransferases from four separate Japanese families with 2,8-dihydroxyadenine urolithiasis associated with partial enzyme deficiencies
S Fujimori, I Akaoka, K Sakamoto, H Yamanaka, K Nishioka, N Kamatani
Human Genetics 1985
Inherited disorders of purine metabolism — Underlying molecular mechanisms
W Gutensohn
Klinische Wochenschrift 1984
Structure, expression, and mutation of the hypoxanthine phosphoribosyltransferase gene
DW Melton, DS Konecki, J Brennand, CT Caskey
Proceedings of the National Academy of Sciences 1984
Progress in Nucleic Acid Research and Molecular Biology
FS Collins, SM Weissman
Progress in nucleic acid research and molecular biology 1984
Mutation, Cancer, and Malformation
EH Chu, WM Generoso
1984
Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency: The Molecular Basis of the Clinical Syndromes
JS Flier, MJ Moore, JM Wilson, AB Young, WN Kelley
New England Journal of Medicine 1983
Verhandlungen der Deutschen Gesellschaft für Innere Medizin
B Schlegel
1962

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