C1 inhibitor mutations which affect intracellular transport and secretion in type I hereditary angioedema.
A cluster of point mutations was found in the region of exon 8 of the C1 INH gene which codes for the 28 C-terminal amino acids. Seven of these mutations introduce amino acid changes and one results in a stop codon. Upon transient expression in monkey kidney Cos-7 cells all of these C1 inhibitor mutants showed an impaired intracellular transport and most of them failed to be secreted. Biochemical and immunofluorescence studies indicated that the defective proteins accumulate or are degraded mainly in the endoplasmic reticulum. The product of deletions of exons 4, which has an internal in frame deletion of 45 amino acids, also fails to be secreted.
Verpy
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Unité d'Immunogénétique, Institut Pasteur, Paris, France.
Couture-Tosi
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Tosi
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D000595:Amino Acid Sequence; D000799:Angioedema / Q000097:blood / Q000235:genetics*; D003062:Codon; D003174:Complement C1 Inactivator Proteins / Q000235:genetics* / Q000378:metabolism*; D005091:Exons; D006801:Humans; D017354:Point Mutation; D017384:Sequence Deletion
D003062:Codon; D003174:Complement C1 Inactivator Proteins