Summary
A deficiency in the activity of uroporphyrinogen decarboxylase (UROD), the fifth enzyme of the haem biosynthetic pathway, is found in familial porphyria cutanea tarda (F-PCT) and hepatoerythropoietic porphyria (HEP). A new mutation (R292G) and a deletion have been found in a pedigree with two HEP patients (two sisters). The R292G mutation was not detected in 13 unrelated affected patients with F-PCT, so it appears to be uncommon. The possibility that the arginine 292 may participate at the active site of the enzyme is discussed. A summary of the 7 mutations/deletions found in the UROD gene with their frequency is presented.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Dailey HA, Fleming JE (1986) The role of arginyl residues in porphyring binding to ferrochelatase. J Biol Chem 261:7902–7905
Elder GH, Smith SG, Herrero C, Lecha M, Mascaro JM, Muniesca AM, Czornecki DB, Brenau J, Poulos V, De Salamanca RE (1981) Hepatoerythropoietic porphyria: a new uroporphyrinogen decarboxylase defect or homozygous porphyria cutanea tarda? Lancet 1:916–919
Fujita H, Sassa S, Toback AC, Kappas A (1987) Immunochemical study of uroporphyrinogen decarboxylase in a patient with mild hepatoerythropoietic porphyria. J Clin Invest 79:1533–1537
Garey JR, Hansen JL, Harrison LM, Kennedy JB, Kushner JP (1989) A point mutation in the coding region of uroporphyrinogen decarboxylase associated with familial porphyria cutanea tarda. Blood 73:892–895
Garey JR, Harrison LM, Franklin KF, Metcalf KM, Radisky ES, Kushner JP (1990) Uroporphyrinogen decarboxylase: a splice site mutation causes the deletion of exon 6 in multiple families with porphyria cutanea tarda. J Clin Invest 86:1416–1422
Gibbs PNB, Jordan PM (1986) Identification of lysine at the active site of human 5-aminolevulinate dehydratase. Biochem J 236:447–451
Grandchamp B, Picat C, Rooij F de, Beaumont C, Wilson P, Deybach JC, Nordmann Y (1989) A point mutation G-A in exon 12 of the porphobilinogen deaminase gene results in exon skipping and is responsible for acute intermittent porphyria. Nucleic Acids Res 17:6637–6642
Hart GJ, Battersby AR (1985) Purification and properties of uroporphyrinogen III synthase from Englena gracilis. Biochem J 232:151–160
Kappas A, Sassa S, Galbraith RA, Nordmann Y (1988) The porphyrias. In: Stanbury JB (ed) The metabolic basis of inherited disease. McGraw-Hill, New York, pp 1305–1365
Kawanishi S, Keki Y, Sano S (1983) Uroporphyrinogen decarboxylase: purification, properties and inhibition by polychlorinated biphenyl isomers. J Biol Chem 258:4285–4292
Kiel JA, Boels JM, Beldman G, Venema G (1990) Nucleotide sequence of the Synechococcus sp. PCC7942 branching enzyme gene: expression in Bacillus subtilis. Gene 89:77–84
Koszo F, Elder GH, Roberts A, Simon N (1990) Uroporphyrinogen decarboxylase deficiency in hepatoerythropoietic porphyria: further evidence for genetic heterogeneity. Br J Dermatol 122:365–370
Kushner JP, Barbuto AJ, Lee GR (1976) An inherited enzymatic defect in porphyria cutanea tarda. J Clin Invest 58:1089–1097
Lazaro P, De Salamanca RE, Elder GH, Villaseca ML, Schinarro S, Jaqueti G (1984) Is hepatoerythropoietic porphyria a homozygous form of porphyria cutanea tarda? Br J Dermatol 110:613–617
Miller AD, Packman LC, Hart GJ, Alefounder PR, Abell C, Battersby AR (1989) Evidence that pyridoxal phosphate modification of lysine residues (Lys-55 and Lys-59) causes inactivation of hydroxymethylbilane synthase (porphobilinogen deaminase). Biochem J 262:119–124
Romana M, Dubart A, Beaupain D, Chabret C, Goossens M, Romeo PH (1987) Structure of the gene for human Uroporyrinogen decarboxylase. Nucleic Acids Res 15:7343–7356
Romana M, Le Boulch P, Romeo PH (1987) Rat uroporphyrino gen decarboxylase cDNA: nucleotide sequence and comparison to human uroporphyrinogen decarboxylase. Nucleic Acids Res 15:7211
Romana M, Grandchamp B, Dubart A, Amselem S, Chabret C, Nordmann Y, Goossens M, Romeo PH (1991) Identification of a new mutation responsible for hepatoerythropoietic porphyria. Eur J Clin Invest 21:225–229
Romeo PH, Raich N, Dubart A, Beaupain D, Pryor M, Kushner J, Cohen-Solal M, Goossens M (1986) Molecular cloning and nucleotide sequence of a complete human uroporphyrinogen decarboxylase cDNA. J Biol Chem 261:9825–9831
Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory manual, 2nd edn. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY
Sassa S, Verneuil H de, Anderson KE, Kappas A (1983) Purification and properties of human erythrocyte uroporphyrinogen decarboxylase: immunological demonstration of the enzyme defect in porphyria cutanea tarda. Trans Assoc Am Physicians 96:65–75
Straka JG, Kushner JM (1983) Purification and characterization of bovine hepatic uroporphyrinogen decarboxylase. Biochemistry 22:4664–4672
Toback AC, Sassa S, Poh-Fitzpatrick MB, Scheeter J, Saider E, Harber LC, Kappas A (1987) Hepatoerythropoietic porphyria: clinical, biochemical and enzymatic studies in a three generation family lineage. N Engl J Med 316:645–647
Verneuil H de, Aitken G, Nordmann Y (1978) Familial and sporadic porphyria cutanea tarda: two different diseases. Hum Genet 44:145–151
Verneuil H de, Grandchamp B, Nordmann Y (1980) Some kinetic properties of human red cell uroporphyrinogen decarboxylase. Biochim Biophys Acta 611:174–186
Verneuil H de, Sassa S, Kappas A (1983) Purification and properties of uroporphyrinogen decarboxylase from human erythrocytes. J Biol Chem 258:2454–2460
Verneuil H de, Beaumont C, Deybach JC, Nordmann Y, Sfar Z, Kastally R (1984) Enzymatic and immunologic studies of uroporphyrinogen decarboxylase in familial porphyria cutanea tarda and hepatoerythropoietic porphyria. Am J Hum Genet 36:613–622
Verneuil H de, Grandchamp B, Beaumont C, Picat C, Nordmann Y (1986) Uroporphyrinogen decarboxylase structural mutant (Gly281Glu) in a case of porphyria. Science 234:732–734
Verneuil H de, Beaumont C, Grandchamp B, Phung N, Nordmann Y (1986) Molecular heterogeneity of uroporphyrinogen decarboxylase deficiency in hepatoerythropoietic porphyria. In: Nordmann Y (ed) Porphyrins and porphyrias. JohnLibbey Eurotext, Paris, pp 201–208
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
de Verneuil1, H., Bourgeois, F., de Rooij, F. et al. Characterization of a new mutation (R292G) and a deletion at the human uroporphyrinogen decarboxylase locus in two patients with hepatoerythropoietic porphyria. Hum Genet 89, 548–552 (1992). https://doi.org/10.1007/BF00219182
Received:
Revised:
Issue date:
DOI: https://doi.org/10.1007/BF00219182
