Molecular defects of uroporphyrinogen decarboxylase in a patient with mild hepatoerythropoietic porphyria.
The molecular defect of uroporphyrinogen decarboxylase (UROD) was examined in a patient with mild hepatoerythropoietic porphyria. To elucidate the UROD defect, we cloned UROD cDNAs from EBV-transformed lymphoblastoid cells of the proband using reverse transcriptase-polymerase chain reaction. Nucleotide sequence analysis of the cloned UROD cDNAs revealed two separate missense mutations, each occurring in a separate allele. One mutation was a Val134-->Gln transition, and was due to three sequential point mutations (T417G418T419-->CCA); the other mutation was a His220-->Pro transition (A677-->C). UROD phenotype studies demonstrated that the TGT-->CCA mutation was inherited from the father, and the A-->C mutation was inherited from the mother. In contrast to the null activity previously described for a mutant UROD from a patient with familial porphyria cutanea tarda, these mutant URODs had subnormal but substantial enzyme activities, when expressed in Chinese hamster ovary cells. This is the first demonstration of a mutation caused by three sequential base substitutions.
Meguro
K
K
Rockefeller University Hospital.
Fujita
H
H
Ishida
N
N
Akagi
R
R
Kurihara
T
T
Galbraith
R A
RA
Kappas
A
A
Zabriskie
J B
JB
Toback
A C
AC
Harber
L C
LC
D000328:Adult; D001483:Base Sequence; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D017092:Porphyria, Erythropoietic / Q000201:enzymology*; D017121:Porphyria, Hepatoerythropoietic / Q000201:enzymology*; D014575:Uroporphyrinogen Decarboxylase / Q000235:genetics* / Q000378:metabolism*
D014575:Uroporphyrinogen Decarboxylase