Abstract.
 Carboxypeptidase N (EC 3.4.17.3) regulates the activity of peptides such as kinins and anaphylatoxins. Although deficiency of carboxypeptidase N (MIM 212070) produces a severe allergic syndrome, no human mutations have ever been described. Therefore, using archival genomic DNA from a subject with documented carboxypeptidase N deficiency, we sequenced CPN1 (MIM 603103), which encodes the catalytic subunit of carboxypeptidase N. In the genomic DNA of the proband, we discovered three CPN1 variants: (1) 385fsInsG, a frameshift mutation in exon 1 due to a single G insertion at nucleotide 385; (2) 746G>A single-nucleotide polymorphism (SNP), a missense mutation in exon 3 that predicted substitution of aspartic acid for the wild-type conserved glycine at amino acid 178 (G178D); and (3) IVS1 +6C>T, an SNP in intron 1. Among 128 normal Caucasians, the 385fsInsG mutation was absent and the G178D mutation had a frequency of 0.0078, suggesting that these were rare molecular events that likely contributed to the carboxypeptidase N deficiency phenotype. The frequency of the IVS1 +6C>T polymorphism was 0.051. The reagents described here provide tools for further study of association with clinical and biochemical phenotypes related to allergy and immunity.
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Received: November 5, 2002 / Accepted: November 7, 2002
Acknowledgments Dr. Hegele holds a Canada Research Chair (Tier I) in Human Genetics and a Career Investigator award from the Heart and Stroke Foundation of Ontario. This work was supported by grants from Canadian Institutes for Health Research (MT13430), the Canadian Genetic Diseases Network, and the Blackburn Group.
Correspondence to:R.A. Hegele
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Cao, H., Hegele, R. DNA polymorphism and mutations in CPN1, including the genomic basis of carboxypeptidase N deficiency. J Hum Genet 48, 20–22 (2003). https://doi.org/10.1007/s100380300003
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DOI: https://doi.org/10.1007/s100380300003
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