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Carboxypeptidase N deficiency is an autosomal recessive disorder marked by severe allergic reactions due to impaired regulation of kinins and anaphylatoxins. In a single published case, sequencing of CPN1 identified two rare coding variants in trans: c.173dup (p.His59fs) and c.533G>A (p.Gly178Asp) in a proband with documented enzyme deficiency, neither variant being present (frameshift) or found at >0.78% (missense) in 128 controls (PMID:12560874). No additional affected relatives or families have been reported, and segregation studies are lacking. Functional assessment was limited to allele frequency analysis without in vitro or in vivo assays of enzyme activity. No conflicting evidence has been described to date. Overall, current data support a limited level of clinical validity for CPN1 in carboxypeptidase N deficiency. Key Take-home: Identification of biallelic rare CPN1 variants can confirm the diagnosis of carboxypeptidase N deficiency in patients with severe allergic phenotypes.
Gene–Disease AssociationLimitedSingle proband with biallelic CPN1 variants, no segregation or replication ([PMID:12560874]). Genetic EvidenceLimitedOne autosomal recessive case with two rare CPN1 coding variants identified in exon 1 and exon 3 ([PMID:12560874]). Functional EvidenceLimitedAllele frequency analysis in 128 controls only; no functional assays of enzyme activity. |