Analysis of uroporphyrinogen decarboxylase complementary DNAs in sporadic porphyria cutanea tarda.
BACKGROUND
Sporadic porphyria cutanea tarda (S-PCT) has been considered an acquired disease because of the generation of liver-specific inhibitors of uroporphyrinogen decarboxylase (URO-D) activity. Several families have been described with S-PCT in multiple generations, raising the possibility of an inherited basis for the disease. To determine if S-PCT is associated with mutant URO-Ds that might be sensitive to liver-specific inhibitors, a molecular analysis of genomic and hepatocellular URO-Ds was undertaken.


METHODS
Total RNA from lymphoid cell lines from three unrelated patients with S-PCT and poly A+ RNA from liver biopsy samples from two additional patients was used as a template for single-stranded cDNA synthesis, and URO-D sequences were amplified and sequenced. DNA prepared from peripheral blood leukocytes was used as a template to polymerase chain reaction (PCR) amplify the promoter region of the URO-D gene. Sequencing of PCR products was performed completely in both directions by the chain termination method using a variety of custom oligonucleotide primers.


RESULTS
Ten URO-D alleles were sequenced, and no mutations were found. The promoter region of the URO-D gene was also normal.


CONCLUSIONS
It is concluded that S-PCT is not due to mutations at the URO-D locus. If inherited factors are involved, other loci must be affected.
Garey
J R
JR
Department of Medicine, University of Utah School of Medicine, Salt Lake City.
Franklin
K F
KF
Brown
D A
DA
Harrison
L M
LM
Metcalf
K M
KM
Kushner
J P
JP
D000328:Adult; D000368:Aged; D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics*; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D017119:Porphyria Cutanea Tarda / Q000201:enzymology* / Q000235:genetics; D014575:Uroporphyrinogen Decarboxylase / Q000235:genetics* / Q000378:metabolism
D004247:DNA; D014575:Uroporphyrinogen Decarboxylase