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Mutations in the translation initiation codon of the protoporphyrinogen oxidase gene underlie variegate porphyria
Author(s) -
Jorge Frank,
John A. McGrath,
Maureen B. Poh–Fitzpatrick,
J.L.M. Hawk,
Angela M. Christiano
Publication year - 1999
Publication title -
clinical and experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.587
H-Index - 78
eISSN - 1365-2230
pISSN - 0307-6938
DOI - 10.1046/j.1365-2230.1999.00484.x
Subject(s) - protoporphyrinogen oxidase , transversion , missense mutation , biology , microbiology and biotechnology , methionine , gene , genetics , mutation , translation (biology) , amino acid , messenger rna
Variegate porphyria (VP), one of the acute hepatic porphyrias, is characterized by a reduced catalytic activity of protoporphyrinogen oxidase (PPO), the penultimate enzyme in the porphyrin–haem biosynthetic pathway. VP has been linked to the PPO gene on chromosome 1q22‐23, and several mutations underlying this disorder have been described recently. In this study, we identified two different missense mutations in the translation initiation codon of the PPO gene in two unrelated patients with VP. Mutation analysis was carried out using PCR, heteroduplex analysis, automated sequencing, and restriction enzyme digestion. In the first patient, the results revealed an A‐to‐T transversion (ATG → TTG), resulting in the substitution of methionine by leucine (M1L). The mutation detected in the second patient was a T‐to‐C transition (ATG → ACG), leading to the conversion of methionine to threonine (M1T). These mutations abolish the initiation of translation at the normal site, and consequently, translation of an abnormal messenger RNA (mRNA) would result in the synthesis of a truncated PPO protein lacking the amino terminus.