Context Hereditary pancreatitis is an autosomal dominant disease which is caused by mutations in the PRSS1 gene. Objective The aim of our study was to describe the penetrance and phenotype-genotype correlations of the c.346C>T (p.R122C) mutation. Design Case series descriptive study. Patients Forty-one members of six families from whom DNA samples were analyzed. Main outcome measures In subjects with R122C mutation symptoms, pancreatic calcifications, main pancreatic duct changes, diabetes, steatorrhea, pancreatic cancer and surgery were recorded. Results The R122C mutation was detected in 22 of the 41 family members studied, and 7 men and 2 women developed pancreatic disease, resulting in a penetrance of 40.9%. One out of the 9 patients was excluded because she died before the mutation was detected. The mean age at symptom onset was 23.5 years (range: 4-51 years). Abdominal pain was present in 6 (75.0%) of the 8 patients with the R122C mutation who developed pancreatic disease. Calcifications had developed in 5 (62.5%) at a mean age of 35.8 years (range: 14-56 years). Five (62.5%) developed changes in the pancreatic ducts at a mean age of 44.2 years (range: 19-65 years). Two patients (25.0%) developed steatorrhea during the follow-up at 26 and 35 years of disease progression. Diabetes developed in five patients (62.5%) at a mean age of 41.4 years old (range: 22-53 years). Three of the patients analyzed (37.5%) developed pancreatic cancer at 59 years of age, 63 years of age and 70 years of age. Conclusions Penetrance of the R122C mutation is lower than that described for the R122H and N29I mutations, and there is a tendency toward a predominance of males with the R122C mutation who developed the phenotype of pancreatitis.
Gonzalo de las Heras-Castaño, Beatriz Castro-Senosiaín, Ana Fontalba, Marcos López-Hoyos, Pascual Sánchez-Juán