Targeted Gene Next-Generation Sequencing in Chinese Children with Chronic Pancreatitis and Acute Recurrent Pancreatitis - 23/11/17
Abstract |
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.
Le texte complet de cet article est disponible en PDF.Keywords : chronic pancreatitis, acute recurrent pancreatitis, PRSS1, SPINK1, CFTR, next-generation sequencing
Abbreviations** : ATP8B1, CASR, CFTR, CLDN2, CP, CPA1, CTRC, CTSB, HGMD, KRT8, PRSS1, SNV, SPINK1
Plan
| Supported by the Science and Technology Fund Project of Shanghai Jiao Tong University School of Medicine (Project No.: 14XJ10013). The authors declare no conflicts of interest. |
Vol 191
P. 158 - décembre 2017 Retour au numéro
Article précédent
- Persistent High Non-High-Density Lipoprotein Cholesterol in Early Childhood: A Latent Class Growth Model Analysis
- Jordan M. Albaum, Sarah Carsley, Yang Chen, David W.H. Dai, Gerald Lebovic, Brian W. McCrindle, Jonathon L. Maguire, Patricia C. Parkin, Catherine S. Birken, TARGet Kids! Collaboration
- The Benefits of Early Oral Nutrition in Mild Acute Pancreatitis
- Kate M. Ellery, Soma Kumar, Wallace Crandall, Cheryl Gariepy
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?