Summary
Pancreatitis can result from a combination of both genetic and non-genetic factors. Some genetic variants are highly penetrant, while others act as low penetrance “disease modifying” contributors, making results difficult to interpret. To better understand the inheritance patterns and complexity of results,, we reviewed genetic testing results from more than 400 individuals with suspected hereditary pancreatitis having received Blueprint Genetics “Pancreatitis” next generation sequencing panel that included sequencing and copy number analysis. Key findings include that
- In this cohort, 21% of patients carried ≥1 pathogenic, likely pathogenic, or risk factor variant, associated with pancreatitis
- Approximately 75% of these results followed a complex pattern of inheritance- including multigene findings and mixed autosomal dominant/recessive inheritance patterns
- The most frequently identified variants were SPINK1 risk factor alleles, CFTR single heterozygous variants, and PRSS1 P/LP variants.
These results illustrate the genetic complexity of the genetics of pancreatitis and underscore the importance of expert genetic counseling to support accurate test result interpretation.
Authors:
Julie Hathaway, Emily Partack, Emma Martensson, Whitney Dodge, Allison Sluyters, Inka Saarinen, Marcos Cicerchia, Saija Ahonen, Milja Kaare, Tiia Kangas-Kontio, Lotta Koskinen, Ville Kytölä, Janica Djupsjöbacka, Massimiliano Gentile, Pertteli Salmenperä, Jussi Paananen, Samuel Myllykangas, Juha Koskenvuo