Transinhibition of C1 inhibitor synthesis in type I hereditary angioneurotic edema

Judit Kramer, Fred S. Rosen, Harvey R. Colten, Katalin Rajczy, Robert C. Strunk

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51 Citations (Scopus)

Abstract

To ascertain the mechanism for decreased synthesis of C1 inhibitor (C1 INH) in certain patients with the autosomal dominant disorder hereditary angioneurotic edema, we studied expression of C1 INH in fibroblasts in which the mutant and wild type mRNA and protein could be distinguished because of deletion of exon 7 (ΔE×7). In the HANE ΔE×7 cells, the amount of wild type mRNA (2.1 kb) was expressed at 52±2% (n = 5) of normal, whereas the mutant mRNA was 17±1% (n = 5)of normal. Rates of synthesis of both wild type and mutant proteins (11±3 and 3±1% of normal, respectively) were lower than predicted from the mRNA levels. There was no evidence of increased C1 INH protein catabolism. These data indicate that there are multiple levels of control of C1 INH synthesis in type I hereditary angioneurotic edema. Pretranslational regulation results in < 50% of the mutant truncated 1.9-kb mRNA. In addition, translational regulation results in decreased synthesis of both wild type and mutant C1 INH proteins. These data suggest a transinhibition of wild type C1 INH translation by mutant mRNA and/or protein.

Original languageEnglish
Pages (from-to)1258-1262
Number of pages5
JournalJournal of Clinical Investigation
Volume91
Issue number3
DOIs
Publication statusPublished - Mar 1993

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Keywords

  • C1 inhibitor
  • Hereditary angioneurotic edema
  • Synthesis
  • Transinhibition
  • Translation

ASJC Scopus subject areas

  • Medicine(all)

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