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Xenobiotic_sensitivity Report for: Defect in hydroxylation of diphenylhydantoin

Alternative name(s)|Defect in microsomal xenobiotic epoxide hydrolase
Phenytoin toxicity
Arene oxide detoxification defect
Fetal hydantoin syndrome
Defect in hydroxylation of diphenylhydantoin
Diphenylhydantoin toxicity
Defect in detoxification of aflatoxin B1
Mutation|1 mutation:
OMIM: |132810

(from OMIM) Epoxide hydrolases (EC ) play an important role in both the activation and detoxification of exogenous chemicals such as polycyclic aromatic hydrocarbons. Strickler et al. (1985) hypothesized a mutant form of microsomal epoxide hydrolase as the molecular basis for abnormal reactions to phenytoin and some other drugs. Phenytoin (diphenylhydantoin, dilantin) is metabolized by cytochrome P-450 monooxygenases to several oxidized products, including parahydroxylated and dihydrodiol metabolites. Arene oxides, which are reactive electrophilic compounds, are intermediates in these oxidative reactions. If not detoxified, arene oxide metabolites can covalently bind to cell macromolecules, resulting in cell death, mutation, tumors, birth defects, and, by acting as haptens, can lead to secondary immune phenomena.

    Title: Epoxid hydrolase single gene polymorphism (RS1051740) and severity of chronic obstructive disease
    Antonova I, Gridnyev O, Galchinskaya V
    Ref: Wiad Lek, 75:2779, 2022 : PubMed


    Title: Fetal hydantoin syndrome with unilateral atypical cleft hand: additional evidence for vascular disruption
    De Smet L, Debeer P
    Ref: Genet Couns, 13:157, 2002 : PubMed


    Title: Genetic polymorphisms of biotransformation enzymes in patients with Hodgkin's and non-Hodgkin's lymphomas
    Sarmanova J, Benesova K, Gut I, Nedelcheva-Kristensen V, Tynkova L, Soucek P
    Ref: Hum Mol Genet, 10:1265, 2001 : PubMed


    Title: A polymorphism in the gene for microsomal epoxide hydrolase is associated with pre-eclampsia
    Zusterzeel PL, Peters WH, Visser W, Hermsen KJ, Roelofs HM, Steegers EA
    Ref: Journal of Medical Genetics, 38:234, 2001 : PubMed


    Title: Targeted disruption of the microsomal epoxide hydrolase gene. Microsomal epoxide hydrolase is required for the carcinogenic activity of 7,12-dimethylbenz[a]anthracene
    Miyata M, Kudo G, Lee YH, Yang TJ, Gelboin HV, Fernandez-Salguero P, Kimura S, Gonzalez FJ
    Ref: Journal of Biological Chemistry, 274:23963, 1999 : PubMed


    Title: Assignment1 of microsomal epoxide hydrolase (EPHX1) to human chromosome 1q42.1 by in situ hybridization
    Hartsfield JK, Jr., Sutcliffe MJ, Everett ET, Hassett C, Omiecinski CJ, Saari JA
    Ref: Cytogenet Cell Genet, 83:44, 1998 : PubMed


    Title: Hand anomalies in fetal-hydantoin syndrome: from nail/phalangeal hypoplasia to unilateral acheiria
    Sabry MA, Farag TI
    Ref: American Journal of Medicine Genet, 62:410, 1996 : PubMed


    Title: Susceptibility to hepatocellular carcinoma is associated with genetic variation in the enzymatic detoxification of aflatoxin B1
    McGlynn KA, Rosvold EA, Lustbader ED, Hu Y, Clapper ML, Zhou T, Wild CP, Xia XL, Baffoe-Bonnie A and Buetow KH <4 more author(s)>
    Ref: Proc Natl Acad Sci U S A, 92:2384, 1995 : PubMed


    Title: Human microsomal epoxide hydrolase: genetic polymorphism and functional expression in vitro of amino acid variants
    Hassett C, Aicher L, Sidhu JS, Omiecinski CJ
    Ref: Hum Mol Genet, 3:421, 1994 : PubMed


    Title: The human microsomal epoxide hydrolase gene (EPHX1): complete nucleotide sequence and structural characterization
    Hassett C, Robinson KB, Beck NB, Omiecinski CJ
    Ref: Genomics, 23:433, 1994 : PubMed


    Title: Familial occurrence of hypersensitivity to phenytoin
    Gennis MA, Vemuri R, Burns EA, Hill JV, Miller MA, Spielberg SP
    Ref: American Journal of Medicine, 91:631, 1991 : PubMed


    Title: Prenatal prediction of risk of the fetal hydantoin syndrome
    Buehler BA, Delimont D, van Waes M, Finnell RH
    Ref: N Engl J Med, 322:1567, 1990 : PubMed


    Title: Human microsomal xenobiotic epoxide hydrolase. Complementary DNA sequence, complementary DNA-directed expression in COS-1 cells, and chromosomal localization
    Skoda RC, Demierre A, McBride OW, Gonzalez FJ, Meyer UA
    Ref: Journal of Biological Chemistry, 263:1549, 1988 : PubMed


    Title: Inheritance of poor phenytoin parahydroxylation capacity in a Dutch family
    Vermeij P, Ferrari MD, Buruma OJ, Veenema H, de Wolff FA
    Ref: Clinical Pharmacology & Therapeutics, 44:588, 1988 : PubMed


    Title: Possible prenatal hydantoin effect in a child born to a nonepileptic mother
    Chodirker BN, Chudley AE, Reed MH, Persaud TV
    Ref: American Journal of Medicine Genet, 27:373, 1987 : PubMed


    Title: Elevated glucocorticoid receptor levels in lymphocytes of children with the fetal hydantoin syndrome (FHS)
    Goldman AS, Van Dyke DC, Gupta C, Katsumata M
    Ref: American Journal of Medicine Genet, 28:607, 1987 : PubMed


    Title: Nucleotide and deduced amino acid sequence of human liver microsomal epoxide hydrolase
    Jackson MR, Craft JA, Burchell B
    Ref: Nucleic Acids Research, 15:7188, 1987 : PubMed


    Title: Microsomal epoxide hydrolase activity in human x mouse hybrid cells
    Brown S, Chalmers DE
    Ref: Biochemical & Biophysical Research Communications, 137:775, 1986 : PubMed


    Title: Genetic predisposition to phenytoin-induced birth defects
    Strickler SM, Dansky LV, Miller MA, Seni MH, Andermann E, Spielberg SP
    Ref: Lancet, 2:746, 1985 : PubMed


    Title: Impairment of phenytoin parahydroxylation as a cause of severe intoxication
    de Wolff FA, Vermeij P, Ferrari MD, Buruma OJ, Breimer DD
    Ref: Ther Drug Monit, 5:213, 1983 : PubMed


    Title: Discordant expression of fetal hydantoin syndrome in a pair of dizygotic twins with different fathers. (Abstract)
    Phelan MC, Pellock JM, Nance WE
    Ref: American Journal of Human Genetics, 33:e67A, 1981 : PubMed


    Title: Predisposition to phenytoin hepatotoxicity assessed in vitro
    Spielberg SP, Gordon GB, Blake DA, Goldstein DA, Herlong HF
    Ref: N Engl J Med, 305:722, 1981 : PubMed


    Title: Inheritance of phenytoin hypometabolism: a kinetic study of one family
    Vasko MR, Bell RD, Daly DD, Pippenger CE
    Ref: Clinical Pharmacology & Therapeutics, 27:96, 1980 : PubMed


    Title: Pharmacogenetics: multiple interactions between genes and environment as determinants of drug response
    Vesell ES
    Ref: American Journal of Medicine, 66:183, 1979 : PubMed


    Title: Inheritance of diphenylhydantoin hypometabolism: a pharmacokinetic study of one family. (Abstract)
    Vasko MR, Bell RD, Daly DD
    Ref: Clinical Pharmacology & Therapeutics, 21:120, 1977 : PubMed


    Title: Risks to the offspring of women treated with hydantoin anticonvulsants, with emphasis on the fetal hydantoin syndrome
    Hanson JW, Myrianthopoulos NC, Harvey MA, Smith DW
    Ref: J Pediatr, 89:662, 1976 : PubMed


    Title: Diphenylhydantoin intoxication attendant to slow inactivation of isoniazid
    Brennan RW, Dehejia H, Kutt H, Verebely K, McDowell F
    Ref: Neurology, 20:687, 1970 : PubMed


    Title: Diphenylhydantoin intoxication. A complication of isoniazid therapy
    Kutt H, Brennan R, Dehejia H, Verebely K
    Ref: Am Rev Respir Dis, 101:377, 1970 : PubMed


    Title: Inhibition of diphenylhydantoin metabolism in rats and in rat liver microsomes by antitubercular drugs
    Kutt H, Verebely K, McDowell F
    Ref: Neurology, 18:706, 1968 : PubMed


    Title: Insufficient Paraphydroxylation as a Cause of Diphenylhydantoin Toxicity
    Kutt H, Wolk M, Scherman R, McDowell F
    Ref: Neurology, 14:542, 1964 : PubMed


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Mail to: Nicolas Lenfant, Thierry Hotelier, Yves Bourne, Pascale Marchot and Arnaud Chatonnet.
Please cite: Lenfant 2013 Nucleic.Acids.Res. or Marchot Chatonnet 2012 Prot.Pept Lett.
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