Molecular defects in ferrochelatase in patients with protoporphyria requiring liver transplantation

The Journal of Clinical Investigation
J R BloomerD A Brenner

Abstract

Protoporphyria is a genetic disorder in which a deficiency of mitochondrial ferrochelatase activity causes accumulation of protoporphyrin that produces severe liver damage in some patients. In this study, mutations of the ferrochelatase gene were examined in eight unrelated patients who had liver transplantation. RNA was prepared from liver and/ or lymphoblasts, and specific reverse transcriptase-nested polymerase chain reactions amplified and sequenced ferrochelatase cDNAs. Products shorter than normal resulted from an exon 3 deletion in three patients, exon 10 deletion in two, exon 2 deletion in one, and deletion of five nucleotides in exon 5 in one. Sequence of normal-size products revealed no other mutations. Western blot showed a reduced quantity of normal-size ferrochelatase protein in protoporphyria liver compared with normal liver (19-51%, mean 32% of normal). Levels of the mitochondrial protein F1-ATPase beta-subunit were not decreased to a similar degree. Liver ferrochelatase activity was reduced more than could be explained by the decrease in ferrochelatase protein (4-20%, mean 9% of normal). These results establish genetic heterogeneity in the most severe phenotype of protoporphyria. However, the gene mutations foun...Continue Reading

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Citations

Oct 22, 2003·Molecular Genetics and Metabolism·Hiba RishegJoseph R Bloomer
Feb 5, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Torsten PlöschFolkert Kuipers
Mar 11, 2005·Journal of Clinical Gastroenterology·Joseph BloomerHiba Risheg
Jul 5, 2006·Journal of Pediatric Gastroenterology and Nutrition·Joseph R BloomerHiba Risheg
Jul 27, 1999·The Journal of Investigative Dermatology·X WangM B Poh-Fitzpatrick
Jun 2, 2011·Experimental Hematology·Yongming WangJoseph R Bloomer
Jul 26, 2003·The Journal of Investigative Dermatology·Wook Lew
Mar 12, 2002·The Journal of Investigative Dermatology·X Schneider-YinE I Minder
May 8, 2008·The British Journal of Dermatology·M ParkerP N Meissner
Mar 27, 2010·Journal of the European Academy of Dermatology and Venereology : JEADV·E I MinderN Schoenfeld
Apr 5, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Ashwani K SingalBrendan M McGuire
Nov 6, 2009·Journal of the European Academy of Dermatology and Venereology : JEADV·J MaJ Wang
Jul 18, 2006·Molecular Genetics and Metabolism·Christian CobboldMichael Badminton
Feb 16, 1999·Biochimica Et Biophysica Acta·S T Magness, D A Brenner
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Jan 25, 2021·Liver International : Official Journal of the International Association for the Study of the Liver·Eva GijbelsLindsey Devisscher

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