title: Hereditary Pancreatitis Associated With the N29T Mutation of the PRSS1 Gene in a Brazilian Family: A Case-Control Study.
abstract: Hereditary pancreatitis (HP) is an autosomal-dominant disease with incomplete penetrance manifesting as early-onset chronic relapsing pancreatitis. A mutation in the PRSS1 gene is present in greater than 70% of HP kindreds and leads to a gain-of-function characterized by the increased autocatalytic conversion of trypsinogen to active trypsin, promoting autodigestion and damage to acinar cells. Other genetic defects observed in the pathogenic mechanism of pancreatitis include mutations in the genes encoding SPINK1, CTRC, and CPA1. There are few reports of HP in Latin America, and no families have been investigated in Brazil. A case-control observational study was conducted at Clementino Fraga Filho University Hospital in Brazil. Patients with suspected HP and healthy controls were enrolled in this study, and a detailed questionnaire was administered to patients with HP. PRSS1 and SPINK1 genes were analyzed by DNA sequencing, and a family that fit the HP diagnostic criteria was identified. The neutral polymorphism c.88-352A > G in the SPINK1 gene was found to be prevalent in the individuals studied, but no important alterations were found in this gene. Ten out of 16 individuals in this family carried the N29T mutation in the PRSS1 gene, with 2 clinically unaffected mutation carriers. The median age of HP onset was 6 years. Pancreatic exocrine failure occurred in 6 patients, 5 of whom also had diabetes mellitus. Surgical procedures were performed on 3 affected members, and no cases of pancreatic cancer have been reported thus far. This study identified the first PRSS1 gene mutation in a Brazilian family with HP.
authors.affiliation: From the Department of Endocrinology, Clementino Fraga Filho University Hospital (MGD, OdCS, FLC); Laboratory of Translational Endocrinology, Institute of Biophysics Carlos Chagas Filho (MGD, JMdM, IDdSS, TMO-C); and Department of Diabetes and Nutrology, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil (MR).
authors.forename: Marcio Garrison
authors.initials: MG
authors.lastname: Dytz
authors.forename: Julia
authors.initials: J
authors.lastname: Mendes de Melo
authors.forename: Olga
authors.initials: O
authors.lastname: de Castro Santos
authors.forename: Isabel Durso
authors.initials: ID
authors.lastname: da Silva Santos
authors.forename: Melanie
authors.initials: M
authors.lastname: Rodacki
authors.forename: Flavia Lucia
authors.initials: FL
authors.lastname: Conceição
authors.forename: Tania Maria
authors.initials: TM
authors.lastname: Ortiga-Carvalho
mesh_terms: D000293:Adolescent; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D006801:Humans; D020125:Mutation, Missense; D010195:Pancreatitis / Q000235:genetics*; D014357:Trypsin / Q000235:genetics*; D014359:Trypsin Inhibitor, Kazal Pancreatic
chemical_list: D002352:Carrier Proteins; C486642:SPINK1 protein, human; D014359:Trypsin Inhibitor, Kazal Pancreatic; C489303:PRSS1 protein, human; D014357:Trypsin