French National Cohort of Patients With PRSS1 Mutations

The diagnosis of hereditary pancreatitis (HP) is based on a genetic criterion - identification of a mutation in the PRSS1 gene - or a genealogical criterion - the presence of chronic pancreatitis in at least 2 first-degree relatives or at least 3 second-degree relatives, in the absence of other identified predisposing factors (in particular chronic alcohol consumption). It is now recommended to look for PH in cases of pancreatitis of unknown origin in young patients or those with a family history.

The first mutation in the PRSS1 gene, R122H, was described in 1996. Today, >100 PRSS1 variants are known. Of these, 26 variants are considered 'pathological' and 51 'benign', with the other variants having a less well-defined clinical outcome. PH is a rare cause of pancreatitis (< 1%). Its prevalence in France is estimated at 0.3/100,000 people.

Because of its rarity, there are few studies to decipher this disease. Fewer than 1,000 patients are affected in France. In practice, there is great variability in the phenotypic expression of mutations, even for a similar mutation in the same family. There is a lack of scientific knowledge, which means that patients with PH cannot be treated optimally.

In this study, patients carrying a PRSS1 mutation will be identified from the patient lists of the three French genetics laboratories (Brest University Hospital, Cochin-Paris University Hospital, Lille University Hospital) carrying out PRSS1 gene analysis. Patients will be included by the doctors currently treating them. The cohort will be updated as new patients are diagnosed, and the completeness of the cases recorded in the database will be checked every 5 years. Patients are seen annually as part of their care, so medical data can be collected at each visit. Questionnaires will be administered every 5 years during a care visit.

The aim of the study is to assess the incidence of pancreatic adenocarcinoma in the cohort and describe the natural history of hereditary pancreatitis linked to a mutation in PRSS1.

Inclusion criteria

• Being a carrier of a known genetic mutation in the PRSS1 gene coding for cationic trypsinogen
• Be followed in one of the participating centers

Exclusion criteria

• Opposition to data collection, expressed by the patient or one of their legal representatives