title: Molecular defects of uroporphyrinogen decarboxylase in a patient with mild hepatoerythropoietic porphyria.
abstract: 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.
authors.affiliation: Rockefeller University Hospital.
authors.forename: K
authors.initials: K
authors.lastname: Meguro
authors.forename: H
authors.initials: H
authors.lastname: Fujita
authors.forename: N
authors.initials: N
authors.lastname: Ishida
authors.forename: R
authors.initials: R
authors.lastname: Akagi
authors.forename: T
authors.initials: T
authors.lastname: Kurihara
authors.forename: R A
authors.initials: RA
authors.lastname: Galbraith
authors.forename: A
authors.initials: A
authors.lastname: Kappas
authors.forename: J B
authors.initials: JB
authors.lastname: Zabriskie
authors.forename: A C
authors.initials: AC
authors.lastname: Toback
authors.forename: L C
authors.initials: LC
authors.lastname: Harber
mesh_terms: 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*
chemical_list: D014575:Uroporphyrinogen Decarboxylase