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CLDN2Hereditary Chronic Pancreatitis

CLDN2 has been proposed as a risk gene for hereditary chronic pancreatitis based on a multi-patient cohort study, but specific proband counts, familial segregation, and variant details were not reported (PMID:34798985). Hereditary chronic pancreatitis exhibits an autosomal dominant inheritance pattern with incomplete penetrance and presents with recurrent abdominal pain (HP:0002027), exocrine pancreatic insufficiency (HP:0001736), endocrine insufficiency manifesting as diabetes mellitus (HP:0011922), and elevated risk of pancreatic neoplasms (HP:0100023). The association of CLDN2 falls within the pancreatic ductal secretion mechanism alongside CTRC, CPA1, and CEL, yet no segregation or functional assays have confirmed a causal role. Additional case-level genotype–phenotype correlations and experimental validation are required to establish the pathogenicity of CLDN2 variants.

Key take-home: CLDN2 remains a candidate gene for hereditary chronic pancreatitis with insufficient genetic and functional evidence to guide clinical decision-making.

References

  • Gastrointestinal endoscopy clinics of North America • 2022 • Genetic Evaluation of Pancreatitis PMID:34798985

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Association based solely on a single cohort study with no proband counts or segregation data ([PMID:34798985]).

Genetic Evidence

Limited

Cohort association without specific variant or family data.

Functional Evidence

Limited

No functional studies evaluating the impact of CLDN2 variants in hereditary chronic pancreatitis.