Molecular Analysis of Uroporphyrinogen Decarboxylase Deficiency in a Family with Two Cases of Hepatoerythropoietic Porphyria

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1986 Feb 1

PMID 3753711

Citations 5

Authors

H de Verneuil

B Grandchamp

P H Romeo

N Raich

C Beaumont

M Goossens

H Nicolas

Y Nordmann

Affiliations

Soon will be listed here.

Abstract

In order to determine the molecular basis of uroporphyrinogen (URO) decarboxylase deficiency responsible for hepatoerythropoietic porphyria (HEP) and familial porphyria cutanea tarda, we used a human URO decarboxylase cDNA to analyze the organization and expression of the URO decarboxylase gene in lymphoblastoid cells from normal individuals and from two patients with HEP. We could detect neither deletions nor rearrangements in the URO decarboxylase gene. Synthesis, processing, and cell-free translation of the specific transcripts appeared to be normal. The half-life of the abnormal protein was 12 times shorter than that of the normal enzyme. The results indicate that the enzyme defect is due to a rapid degradation of the protein in vivo. This study is the first to provide information regarding the molecular mechanism responsible for the URO decarboxylase deficiency in HEP.

Citing Articles

Familial porphyria cutanea tarda: characterization of seven novel uroporphyrinogen decarboxylase mutations and frequency of common hemochromatosis alleles.

Mendez M, Sorkin L, Rossetti M, Astrin K, del C Batlle A, Parera V Am J Hum Genet. 1998; 63(5):1363-75.

PMID: 9792863 PMC: 1377546. DOI: 10.1086/302119.

Immunochemical study of uroporphyrinogen decarboxylase in a patient with mild hepatoerythropoietic porphyria.

Fujita H, Sassa S, Toback A, Kappas A J Clin Invest. 1987; 79(5):1533-7.

PMID: 3571497 PMC: 424431. DOI: 10.1172/JCI112985.

Steady-state levels of uroporphyrinogen decarboxylase mRNA in lymphoblastoid cell lines from patients with familial porphyria cutanea tarda and their relatives.

Hansen J, Pryor M, Kennedy J, Kushner J Am J Hum Genet. 1988; 42(6):847-53.

PMID: 3369447 PMC: 1715209.

Diagnosis of genetic disease using recombinant DNA. Supplement.

Cooper D, Schmidtke J Hum Genet. 1987; 77(1):66-75.

PMID: 3305309 DOI: 10.1007/BF00284717.

The molecular defect of ferrochelatase in a patient with erythropoietic protoporphyria.

Nakahashi Y, Fujita H, Taketani S, Ishida N, Kappas A, Sassa S Proc Natl Acad Sci U S A. 1992; 89(1):281-5.

PMID: 1729699 PMC: 48220. DOI: 10.1073/pnas.89.1.281.

References

de Verneuil H, Beaumont C, Deybach J, Nordmann Y, Sfar Z, Kastally R . Enzymatic and immunological studies of uroporphyrinogen decarboxylase in familial porphyria cutanea tarda and hepatoerythropoietic porphyria. Am J Hum Genet. 1984; 36(3):613-22. PMC: 1684444. View

Romeo P, Dubart A, Grandchamp B, de Verneuil H, Rosa J, Nordmann Y . Isolation and identification of a cDNA clone coding for rat uroporphyrinogen decarboxylase. Proc Natl Acad Sci U S A. 1984; 81(11):3346-50. PMC: 345504. DOI: 10.1073/pnas.81.11.3346. View

White R . DNA in medicine. Human genetics. Lancet. 1984; 2(8414):1257-62. DOI: 10.1016/s0140-6736(84)92806-x. View

Daddona P, Davidson B, Perignon J, Kelley W . Genetic expression in partial adenosine deaminase deficiency. mRNA levels and protein turnover for the enzyme variants in human B-lymphoblast cell lines. J Biol Chem. 1985; 260(6):3875-80. View

AGUADE J, Castells A, INDACOCHEA A, Rodes J . A case of biochemically unclassifiable hepatic porphyria. Br J Dermatol. 1969; 81(4):270-5. DOI: 10.1111/j.1365-2133.1969.tb13979.x. View

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

Pelham H, Jackson R . An efficient mRNA-dependent translation system from reticulocyte lysates. Eur J Biochem. 1976; 67(1):247-56. DOI: 10.1111/j.1432-1033.1976.tb10656.x. View

Kushner J, Barbuto A, Lee G . An inherited enzymatic defect in porphyria cutanea tarda: decreased uroporphyrinogen decarboxylase activity. J Clin Invest. 1976; 58(5):1089-97. PMC: 333275. DOI: 10.1172/JCI108560. View

Elder G, Lee G, Tovey J . Decreased activity of hepatic uroporphyrinogen decarboxylase in sporadic porphyria cutanea tarda. N Engl J Med. 1978; 299(6):274-8. DOI: 10.1056/NEJM197808102990603. View

10.

de Verneuil H, Aitken G, Nordmann Y . Familial and sporadic porphyria cutanea: two different diseases. Hum Genet. 1978; 44(2):145-51. DOI: 10.1007/BF00295407. View

11.

Elder G, Smith S, Herrero C, Lecha M, Mascaro J, Muniesa A . Hepatoerythropoietic porphyria: a new uroporphyrinogen decarboxylase defect or homozygous porphyria cutanea tarda?. Lancet. 1981; 1(8226):916-9. DOI: 10.1016/s0140-6736(81)91615-9. View

12.

Omary M, Trowbridge I . Biosynthesis of the human transferrin receptor in cultured cells. J Biol Chem. 1981; 256(24):12888-92. View

13.

Goossens M, Kan Y . DNA analysis in the diagnosis of hemoglobin disorders. Methods Enzymol. 1981; 76:805-17. DOI: 10.1016/0076-6879(81)76159-7. View

14.

Kawanishi S, Seki Y, Sano S . Uroporphyrinogen decarboxylase. Purification, properties, and inhibition by polychlorinated biphenyl isomers. J Biol Chem. 1983; 258(7):4285-92. View

15.

de Verneuil H, Sassa S, Kappas A . Purification and properties of uroporphyrinogen decarboxylase from human erythrocytes. A single enzyme catalyzing the four sequential decarboxylations of uroporphyrinogens I and III. J Biol Chem. 1983; 258(4):2454-60. View

16.

Wilson J, Baugher B, Mattes P, Daddona P, Kelley W . Human hypoxanthine-guanine phosphoribosyltransferase. Demonstration of structural variants in lymphoblastoid cells derived from patients with a deficiency of the enzyme. J Clin Invest. 1982; 69(3):706-15. PMC: 371029. DOI: 10.1172/jci110499. View

17.

Adrian G, HUTTON J . Adenosine deaminase messenger RNAs in lymphoblast cell lines derived from leukemic patients and patients with hereditary adenosine deaminase deficiency. J Clin Invest. 1983; 71(6):1649-60. PMC: 370370. DOI: 10.1172/jci110920. View

18.

de Verneuil H, Sassa S, Kappas A . Effects of polychlorinated biphenyl compounds, 2,3,7,8-tetrachlorodibenzo-p-dioxin, phenobarbital and iron on hepatic uroporphyrinogen decarboxylase. Implications for the pathogenesis of porphyria. Biochem J. 1983; 214(1):145-51. PMC: 1152219. DOI: 10.1042/bj2140145. View

19.

Elder G, Tovey J, Sheppard D . Purification of uroporphyrinogen decarboxylase from human erythrocytes. Immunochemical evidence for a single protein with decarboxylase activity in human erythrocytes and liver. Biochem J. 1983; 215(1):45-55. PMC: 1152362. DOI: 10.1042/bj2150045. View

20.

Straka J, Kushner J . Purification and characterization of bovine hepatic uroporphyrinogen decarboxylase. Biochemistry. 1983; 22(20):4664-72. DOI: 10.1021/bi00289a009. View