Molecular analysis of uroporphyrinogen decarboxylase deficiency in a family with two cases of hepatoerythropoietic porphyria.

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.

• Authors: H de Verneuil, B Grandchamp, P H Romeo, N Raich, C Beaumont, M Goossens, H Nicolas, Y Nordmann
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 77 Issue 2 Pg. 431-5 (Feb 1986) ISSN: 0021-9738 [Print] United States
• PMID: 3753711 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Messenger
• DNA
• Carboxy-Lyases
• Uroporphyrinogen Decarboxylase

Topics

• Carboxy-Lyases (deficiency)
• Cell Line
• DNA (genetics)
• Erythropoiesis
• Half-Life
• Humans
• Liver Diseases
• Lymphocytes (metabolism)
• Nucleic Acid Hybridization
• Porphyrias (enzymology, genetics)
• Protein Biosynthesis
• RNA, Messenger (genetics)
• Uroporphyrinogen Decarboxylase (deficiency, genetics)