The porphyrias arise from predominantly inherited catalytic deficiencies of specific enzymes in heme biosynthesis. All genes encoding these enzymes have been cloned and several mutations underlying the different types of porphyrias have been reported. Traditionally, the diagnosis of porphyria is made on the basis of clinical symptoms, characteristic biochemical findings, and specific enzyme assays. In some cases however, these diagnostic tools reveal overlapping findings, indicating the existence of dual porphyrias with two enzymes of heme biosynthesis being deficient simultaneously. Recently, it was reported that the so-called Chester porphyria shows features of both variegate porphyria and acute intermittent porphyria. Linkage analysis revealed a novel chromosomal locus on chromosome 11 for the underlying genetic defect in this disease, suggesting that a gene that does not encode one of the enzymes of heme biosynthesis might be involved in the pathogenesis of the porphyrias. After excluding candidate genes within the linkage interval, we identified a nonsense mutation in the porphobilinogen deaminase gene on chromosome 11q23.3, which harbors the mutations causing acute intermittent porphyria, as the underlying genetic defect in Chester porphyria. However, we could not detect a mutation in the coding or the promotor region of the protoporphyrinogen oxidase gene that is mutated in variegate porphyria. Our results indicate that Chester porphyria is neither a dual porphyria, nor a separate type of porphyria, but rather a variant of acute intermittent porphyria. Further, our findings largely exclude the possibility that a hitherto unknown gene is involved in the pathogenesis of the porphyrias.

• MeSH
• akutní intermitentní porfyrie klasifikace   genetika   MeSH
• ferredoxiny genetika   MeSH
• flavoproteiny genetika   MeSH
• hydroxymethylbilansynthasa genetika   MeSH
• lidé MeSH
• mitochondriální proteiny genetika   MeSH
• molekulární sekvence - údaje MeSH
• mutační analýza DNA MeSH
• nesmyslný kodon * MeSH
• protoporfyrinogenoxidasa genetika   MeSH
• sekvence nukleotidů MeSH
• sukcinátdehydrogenasa genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ferredoxiny MeSH
• flavoproteiny MeSH
• hydroxymethylbilansynthasa MeSH
• mitochondriální proteiny MeSH
• nesmyslný kodon * MeSH
• PPOX protein, human MeSH Prohlížeč
• protoporfyrinogenoxidasa MeSH
• SDHD protein, human MeSH Prohlížeč
• sukcinátdehydrogenasa MeSH