Format

Send to

Choose Destination
J Clin Invest. 1998 Jul 1;102(1):107-14.

Molecular defects in ferrochelatase in patients with protoporphyria requiring liver transplantation.

Author information

1
Liver Center at The University of Alabama at Birmingham, Birmingham, Alabama 35294-0005, USA. j_bloomer@gasmac.dom.uab.edu

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 found share the property of causing a major structural alteration in the ferrochelatase protein.

PMID:
9649563
PMCID:
PMC509071
DOI:
10.1172/JCI1347
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for American Society for Clinical Investigation Icon for PubMed Central
Loading ...
Support Center