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Description of a new mutation in hepatoerythropoietic porphyria and prenatal exclusion of a homozygous fetus.
Arch Dermatol. 2002 Jul; 138(7):957-60.AD

Abstract

BACKGROUND

Hepatoerythropoietic porphyria (HEP) is usually a severe form of cutaneous porphyria, characterized biochemically by an increased urinary excretion of polycarboxylated porphyrins. The disease is the result of a profound deficiency (<10% of normal activity) of uroporphyrinogen decarboxylase (UROD) activity. Hepatoerythropoietic porphyria is inherited as an autosomal recessive trait, whereas familial porphyria cutanea tarda is dominant. At least 30 different mutations of the UROD gene have been identified in patients with HEP and familial porphyria cutanea tarda, with 1 predominant missense mutation (glycine-to-glutamic acid substitution at codon 281) in Spanish patients with HEP.

OBSERVATION

A 5-year-old patient with first-degree-related parents presented with HEP and mild symptomatology. We found low levels of UROD enzymatic activity and a new homozygous mutation of the UROD gene, a phenylanine-to-leucine substitution at codon 46 (F46L). Both parents were healthy carriers of the mutation. The mother had reduced UROD activity (50% of normal), whereas the father had normal UROD activity. Prokaryotic expression of the F46L mutation using a pGEX vector has been used to confirm the deleterious effect of the mutation. When the mother started a new pregnancy, a prenatal study showed the absence of F46L mutation in the fetus and no accumulation of porphyrins in the amniotic fluid.

CONCLUSIONS

A new mutation in the UROD gene causes a mild HEP phenotype. A normal UROD enzymatic activity was observed in the father, despite the presence of the heterozygous mutation. To our knowledge, this observation is the first description of a prenatal exclusion of HEP.

Authors+Show Affiliations

Laboratoire de Pathologie Moléculaire et Thérapie Génique, Université Victor Segalen-Bordeaux 2, 146, rue Léo Saignat, 33076 Bordeaux CEDEX, France. Cecile.Ged@pmtg.u-bordeaux2.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12071824

Citation

Ged, Cécile, et al. "Description of a New Mutation in Hepatoerythropoietic Porphyria and Prenatal Exclusion of a Homozygous Fetus." Archives of Dermatology, vol. 138, no. 7, 2002, pp. 957-60.
Ged C, Ozalla D, Herrero C, et al. Description of a new mutation in hepatoerythropoietic porphyria and prenatal exclusion of a homozygous fetus. Arch Dermatol. 2002;138(7):957-60.
Ged, C., Ozalla, D., Herrero, C., Lecha, M., Mendez, M., de Verneuil, H., & Mascaro, J. M. (2002). Description of a new mutation in hepatoerythropoietic porphyria and prenatal exclusion of a homozygous fetus. Archives of Dermatology, 138(7), 957-60.
Ged C, et al. Description of a New Mutation in Hepatoerythropoietic Porphyria and Prenatal Exclusion of a Homozygous Fetus. Arch Dermatol. 2002;138(7):957-60. PubMed PMID: 12071824.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Description of a new mutation in hepatoerythropoietic porphyria and prenatal exclusion of a homozygous fetus. AU - Ged,Cécile, AU - Ozalla,D, AU - Herrero,C, AU - Lecha,M, AU - Mendez,M, AU - de Verneuil,H, AU - Mascaro,J M, PY - 2002/6/20/pubmed PY - 2002/7/30/medline PY - 2002/6/20/entrez SP - 957 EP - 60 JF - Archives of dermatology JO - Arch Dermatol VL - 138 IS - 7 N2 - BACKGROUND: Hepatoerythropoietic porphyria (HEP) is usually a severe form of cutaneous porphyria, characterized biochemically by an increased urinary excretion of polycarboxylated porphyrins. The disease is the result of a profound deficiency (<10% of normal activity) of uroporphyrinogen decarboxylase (UROD) activity. Hepatoerythropoietic porphyria is inherited as an autosomal recessive trait, whereas familial porphyria cutanea tarda is dominant. At least 30 different mutations of the UROD gene have been identified in patients with HEP and familial porphyria cutanea tarda, with 1 predominant missense mutation (glycine-to-glutamic acid substitution at codon 281) in Spanish patients with HEP. OBSERVATION: A 5-year-old patient with first-degree-related parents presented with HEP and mild symptomatology. We found low levels of UROD enzymatic activity and a new homozygous mutation of the UROD gene, a phenylanine-to-leucine substitution at codon 46 (F46L). Both parents were healthy carriers of the mutation. The mother had reduced UROD activity (50% of normal), whereas the father had normal UROD activity. Prokaryotic expression of the F46L mutation using a pGEX vector has been used to confirm the deleterious effect of the mutation. When the mother started a new pregnancy, a prenatal study showed the absence of F46L mutation in the fetus and no accumulation of porphyrins in the amniotic fluid. CONCLUSIONS: A new mutation in the UROD gene causes a mild HEP phenotype. A normal UROD enzymatic activity was observed in the father, despite the presence of the heterozygous mutation. To our knowledge, this observation is the first description of a prenatal exclusion of HEP. SN - 0003-987X UR - https://www.unboundmedicine.com/medline/citation/12071824/Description_of_a_new_mutation_in_hepatoerythropoietic_porphyria_and_prenatal_exclusion_of_a_homozygous_fetus_ L2 - https://jamanetwork.com/journals/jamadermatology/fullarticle/vol/138/pg/957 DB - PRIME DP - Unbound Medicine ER -