Extensive molecular analysis suggested the strong genetic heterogeneity of idiopathic chronic pancreatitis.
Rationale: Genetic features of Chronic Pancreatitis (CP) have been extensively investigated mainly testing genes associated to the trypsinogen activation pathway. However, different molecular pathways involving other genes may be implicated in CP pathogenesis.Objectives:80 patients with Idiopathic CP were investigated using Next Generation Sequencing approach with a panel of 70 genes related to six different pancreatic pathways: premature activation of trypsinogen; modifier genes of Cystic Fibrosis phenotype; pancreatic secretion and ion homeostasis; Calcium signalling and zymogen granules exocytosis; autophagy; autoimmune pancreatitis related genes.Results: We detected mutations in 34 out of 70 genes examined; 64/80 patients (80.0%) were positive for mutations in one or more genes, 16/80 patients (20.0%) had no mutations. Mutations inCFTRwere detected in 32/80 patients (40.0%) and 22 of them exhibited at least one mutation in genes of other pancreatic pathways. Of the remaining 48 patients, 13/80 (16.3%) had mutations in genes involved in premature activation of trypsinogen and 19/80 (23.8%) had mutations only in genes of the other pathways: 38/64 patients positive for mutations showed variants in two or more genes (59.3%).Conclusions:Our data, although to be extended with functional analysis of novel mutations, suggest a high rate of genetic heterogeneity in chronic pancreatitis and that trans-heterozygosity may predispose to the idiopathic CP phenotype.
Laboratory of Medical Genetics, "Bambino Gesù" Children's Hospital, IRCCS, Rome.
Valentina Maria
VM
Sofia
Multifactorial Diseases and Complex Phenotypes Research Area, "Bambino Gesù" Children's Hospital, IRCCS.
Letizia
L
Da Sacco
Laboratory of Medical Genetics, "Bambino Gesù" Children's Hospital, IRCCS.
Cecilia
C
Surace
Laboratory of Medical Genetics, "Bambino Gesù" Children's Hospital.
Anna Cristina
AC
Tomaiuolo
Laboratory of Medical Genetics, "Bambino Gesù" Children's Hospital, IRCCS.
Silvia
S
Genovese
Laboratory of Medical Genetics, "Bambino Gesù" Children's Hospital, IRCCS; Present address: S. Pietro Fatebenefratelli Hospital, UOSD Medical Genetics.
Simona
S
Grotta
Laboratory of Medical Genetics, "Bambino Gesù" Children's Hospital, IRCCS.
Maria
M
Gnazzo
Laboratory of Medical Genetics, "Bambino Gesù" Children's Hospital, IRCCS.
Laura
L
Ciocca
Laboratory of Medical Genetics, "Bambino Gesù" Children's Hospital, IRCCS.
Stefano
S
Petrocchi
Cystic Fibrosis Unit, "Bambino Gesù" Children's Hospital, IRCCS.
Federico
F
Alghisi
Cystic Fibrosis Unit, "Bambino Gesù" Children's Hospital, IRCCS.
Enza
E
Montemitro
Pediatria Sistematica, A.O. Santobono-Pausilipon.
Luigi
L
Martemucci
Ceinge-Biotecnologie avanzate, Naples, Università Telematica Pegaso, Naples, Italy.
Ausilia
A
Elce
Cystic Fibrosis Unit, "Bambino Gesù" Children's Hospital, IRCCS.
Vincenzina
V
Lucidi
Ceinge-Biotecnologie avanzate, Naples, Dipartimento di Medicina Molecolare and Biotecnologie Mediche, Università di Napoli Federico II, Naples, Italy.
Giuseppe
G
Castaldo
Laboratory of Medical Genetics, "Bambino Gesù" Children's Hospital, IRCCS, Viale di San Paolo 15, 00146 Rome, Italy, 0668592536.
Adriano
A
Angioni
gastroenterology; genetics; inflammation; molecular biology; pediatrics