Portal de Periódicos da CAPES

Molecular Defects of Uroporphyrinogen Decarboxylase in a Patient with Mild Hepatoerythropoietic Porphyria

1994; Elsevier BV; Volume: 102; Issue: 5 Linguagem: Inglês

10.1111/1523-1747.ep12374134

1523-1747

Kuniaki Meguro, Hiroyoshi Fujita, Nobuhiro Ishida, Reiko Akagi, Tatsuya Kurihara, Richard A. Galbraith, Attallah Kappas, John B. Zabriskie, Shigeru Sassa, Arnold C. Toback, Leonard C. Harber,

Neonatal Health and Biochemistry

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.