Yuan Xiao1, Wentao Yuan2, Bo Yu3, Yan Guo1, Xu Xu1, Xinqiong Wang1, Yi Yu4, Yi Yu4, Biao Gong5, Chundi Xu6. 1. Pediatric Department, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China. 2. Department of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center and Shanghai Industrial Technology Institute (SITI), Shanghai, China. 3. School of Clinical Medicine, Shanghai University of Medicine & Health Sciences, Shanghai, China. 4. Pediatric Department, Ruijin Hospital North, Shanghai Jiao Tong University, School of Medicine, Shanghai, China. 5. Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China. 6. Pediatric Department, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China; Pediatric Department, Ruijin Hospital North, Shanghai Jiao Tong University, School of Medicine, Shanghai, China. Electronic address: chundixu55@163.com.
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.
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.
Authors: Marta Molina Romero; Alberto Yoldi Chaure; Miguel Gañán Parra; Purificación Navas Bastida; José Luis Del Pico Sánchez; Ángel Vaquero Argüelles; Paloma de la Fuente Vaquero; Juan Pablo Ramírez López; José Antonio Castilla Alcalá Journal: J Assist Reprod Genet Date: 2022-01-29 Impact factor: 3.412
Authors: Chinenye R Dike; Bridget Zimmerman; Yuhua Zheng; Michael Wilschanski; Steven L Werlin; David Troendle; Uzma Shah; Sarah Jane Schwarzenberg; John Pohl; Emily R Perito; Chee Y Ooi; Jaimie D Nathan; Veronique D Morinville; Brian McFerron; Maria Mascarenhas; Asim Maqbool; Quin Liu; Tom K Lin; Sohail Z Husain; Melvin B Heyman; Tanja Gonska; Matthew J Giefer; Cheryl E Gariepy; Douglas S Fishman; Melena Bellin; Bradley Barth; Maisam Abu-El-Haija; Mark E Lowe; Aliye Uc Journal: J Pediatr Gastroenterol Nutr Date: 2020-07 Impact factor: 3.288