ClinGen Dosage Sensitivity Curation Page

PRSS1

  • Curation Status: Complete

Location Information

Select assembly: (NC_000007.13) (NC_000007.14)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity
  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

As gain-of-function intragenic mutations in PRSS1 and a common 605 kb gain involving PRSS1 and PRSS2 are known to cause chronic pancreatitis, it is likely that focal gains in PRSS1 copy number (exclusive of PRSS2 and other genes) will result in a similar phenotype, however such mutations have not yet been reported in patient populations. Note: Mutations associated with hereditary pancreatitis exhibit ~80% penetrance. Here are some reports related to the common gain: PMID17072318: 2006 report of a triplication of a ~605 kb segment containing the PRSS1 and PRSS2 genes in five families with hereditary pancreatitis (HP). PMID18063422: 2008 report of triplication and duplication of the ~605 kb trypsinogen locus in 10 and 4 idiopathic chronic pancreatitis (ICP) patients, respectively. Five naturally occurring trypsinogen locus copy number variants were determined to be artifacts in this study. PMID19584086: 2009 characterization of the ~605 kb trypsinogen locus in 29 triplication carriers (one new family) with HP and 9 duplication carriers (five new patients) with ICP. Array-CGH reveals the presence of an additional ~137 kb segment, containing three known genes and one hypothetical gene, which may also contribute to the phenotypes of these individuals.