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Updated: Feb 18, 2026
Comparative Lesions Analysis Through a Targeted Sequencing Approach
Published on: November 5, 2019
Targeted Gene Next-Generation Sequencing in Chinese Children with Chronic Pancreatitis and Acute Recurrent
Yuan Xiao1, Wentao Yuan2, Bo Yu3
1Pediatric Department, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
Insights
Genetic mutations in PRSS1, SPINK1, and CFTR genes are key causes of pancreatitis in Chinese children. SPINK1 gene mutations may increase the risk of pancreatic duct stones.
Area of Science:
- Genetics
- Pediatrics
- Gastroenterology
Background:
- Pancreatitis, including acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP), can have genetic underpinnings.
- Identifying causative mutations is crucial for understanding disease mechanisms and developing targeted therapies in pediatric patients.
Purpose of the Study:
- To identify causal genetic mutations in children diagnosed with acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP).
- To investigate the association between specific gene mutations and clinical outcomes in pediatric pancreatitis.
Main Methods:
- Next-generation sequencing was employed to analyze nucleotide variations in 10 key genes (PRSS1, SPINK1, CFTR, CTRC, CASR, CTSB, KRT8, CLDN2, CPA1, ATP8B1).
- Clinical characteristics of enrolled patients (55 with CP, 14 with ARP) were investigated.
- Novel mutations were assessed using SIFT2 and Polyphen-2 for predicted effects on protein function.
Main Results:
- Mutations were identified in 45 patients with CP and 10 with ARP.
- Mutations in PRSS1, SPINK1, and CFTR genes were observed in 17 patients.
- SPINK1 mutations were associated with an increased risk of pancreatic duct stones (OR, 11.07; P=.003).
- Patients with CFTR mutations showed significantly higher serum amylase levels (316.0 U/L vs 92.5 U/L; P=.026).
Conclusions:
- Genetic mutations, particularly in PRSS1, SPINK1, and CFTR, represent major etiologies for CP and ARP in Chinese children.
- SPINK1 gene mutations are linked to a higher risk of developing pancreatic duct stones in this pediatric population.
Objective:
To identify causal mutations in certain genes in children with acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP).
Study Design:
After patients were enrolled (CP, 55; ARP, 14) and their clinical characteristics were investigated, we performed next-generation sequencing to detect nucleotide variations among the following 10 genes: cationic trypsinogen protease serine 1 (PRSS1), serine protease inhibitor, Kazal type 1 (SPINK1), cystic fibrosis transmembrane conductance regulator gene (CFTR), chymotrypsin C (CTRC), calcium-sensing receptor (CASR), cathepsin B (CTSB), keratin 8 (KRT8), CLAUDIN 2 (CLDN2), carboxypeptidase A1 (CPA1), and ATPase type 8B member 1 (ATP8B1). Mutations were searched against online databases to obtain information on the cause of the diseases. Certain novel mutations were analyzed using the SIFT2 and Polyphen-2 to predict the effect on protein function.
Results:
There were 45 patients with CP and 10 patients with ARP who harbored 1 or more mutations in these genes; 45 patients had at least 1 mutation related to pancreatitis. Mutations were observed in the PRSS1, SPINK1, and CFTR genes in 17 patients, the CASR gene in 5 patients, and the CTSB, CTRC, and KRT8 genes in 1 patient. Mutations were not found in the CLDN, CPA1, or ATP8B1 genes. We found that mutations in SPINK1 may increase the risk of pancreatic duct stones (OR, 11.07; P = .003). The patients with CFTR mutations had a higher level of serum amylase (316.0 U/L vs 92.5 U/L; P = .026).
Conclusion:
Mutations, especially those in PRSS1, SPINK1, and CFTR, accounted for the major etiologies in Chinese children with CP or ARP. Children presenting mutations in the SPINK1 gene may have a higher risk of developing pancreatic duct stones.
