Hereditary Pancreatitis, PRSS1 Gene Mutation
Conditions
Keywords
hereditary pancreatitis, mutation
Brief summary
The diagnosis of hereditary pancreatitis (PH) is based on a genetic criterion - detection of a mutation in the PRSS1 gene or on a genealogical criterion - the presence of chronic pancreatitis in at least 2 first-degree relatives or at least 3 relatives in the second degree, in the absence of other identified predisposing factors (notably chronic alcohol consumption). It is now recommended to seek PH in cases of pancreatitis of unknown origin in a young patient or with a family history. 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 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.
Detailed description
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.
Interventions
OTHERcollecting their health data from their medical file and completing questionnaires.
Patients seen as part of their follow-up will be offered to participate in the study. Their participation will consist of collecting their health data from their medical file and completing questionnaires.
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the incidence of pancreatic adenocarcinoma | 20 years | Occurrence of pancreatic adenocarcinoma |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Describe the natural history of hereditary pancreatitis linked to a PRSS1 mutation 1/2. | 20 years | Occurrence of endocrine pancreatic insufficiency |
| Describe the natural history of hereditary pancreatitis linked to a PRSS1 mutation 2/2. | 20 years | Occurrence of exocrine pancreatic insufficiency |
| incidence of pancreatic adenocarcinoma in carriers of a PRSS1 mutation to the incidence of pancreatic cancer in the general population in France, estimated from French and international digestive cancer registers 1/2. | 20 years | Occurrence of endocrine pancreatic insufficiency |
| incidence of pancreatic adenocarcinoma in carriers of a PRSS1 mutation to the incidence of pancreatic cancer in the general population in France, estimated from French and international digestive cancer registers.2/2 | 20 years | Occurrence of exocrine pancreatic insufficiency |
| Risk factors associated with progression to adenocarcinoma 1/2 | 20 years | type of PRSS1 mutation. |
| Risk factors associated with progression to adenocarcinoma 2/2 | 20 years | comorbidity |
| Clinical phenotype of patients | 20 years | Collection of clinical characteristics (phenotype) of patients with hereditary pancreatitis. |
| Establish a phenotype-genotype correlation: | 20 years | Assessment of the association between identified genetic mutations and clinical phenotype |
| Calculate the crude and cumulative incidence of exocrine and endocrine pancreatic insufficiency. | 20 years | Occurrence of endocrine pancreatic insufficiency |
| Evaluate the quality of life of patients with hereditary pancreatitis | 20 years | Assessment of patients' quality of life using quality of life questionnaires: SF-36 a |
| Evaluate the quality of life of patients with hereditary pancreatitis, particularly the impact of pain. | 20 years | Pain assessment: Izbicki Pain Score |
Countries
France
Contacts
CONTACTVinciane REBOURS
CONTACTClaude FEREC
PRINCIPAL_INVESTIGATORVinciane REBOURS
APHP
Outcome results
None listed