OBJECTIVES: Defects of PRSS1, SPINK1, CFTR and AAT are considered causative or predisposing to pancreatitis. The aim of this study was to evaluate the impact of these defects into molecular pathology of chronic pancreatitis (CP) and acute recurrent pancreatitis (ARP). METHODS: Ninety-two children with CP or ARP, 55 family members and 50 controls were investigated. The subjects were screened for PRSS1 mutations: R122H, R122C, A16V, N29I; SPINK1 N34S variant; panel of 14 CFTR defects: INNOLiPA CFTR12, CFTRdele2,3 and IVS8-T variant or panel of 3 CFTR defects-F508del, CFTRdele2,3 and IVS8-T; AAT mutations: E264V, E342K. RESULTS: We identified 1 mutated allele in at least 1 of 4 genes in 31 of 92 patients and 12 of 50 controls (P = 0.157). Mutations in SPINK1 and PRSS1 were most frequent. PRSS1 mutations were identified mainly in CP patients (9.6% of CP vs 2.5% of ARP alleles, P = 0.094), whereas N34S SPINK1 mutation was present with comparable frequency in CP and ARP patients (7.7% vs 10.0%, P = 0.768). The frequency of mutations in CFTR alleles was similar to controls (4.9% vs 5%, P = 0.587). Overall frequency of AAT mutations was lower than in the controls. Family studies showed that defects in the examined genes did not always segregate with disease. CONCLUSIONS: PRSS1 defects seem to be causative for pancreatitis, whereas defects in SPINK1 are suggested to be associated with the disease. No association between CFTR mutations and pancreatitis was observed. The importance of AAT variants remains speculative.
OBJECTIVES: Defects of PRSS1, SPINK1, CFTR and AAT are considered causative or predisposing to pancreatitis. The aim of this study was to evaluate the impact of these defects into molecular pathology of chronic pancreatitis (CP) and acute recurrent pancreatitis (ARP). METHODS: Ninety-two children with CP or ARP, 55 family members and 50 controls were investigated. The subjects were screened for PRSS1 mutations: R122H, R122C, A16V, N29I; SPINK1N34S variant; panel of 14 CFTR defects: INNOLiPA CFTR12, CFTRdele2,3 and IVS8-T variant or panel of 3 CFTR defects-F508del, CFTRdele2,3 and IVS8-T; AAT mutations: E264V, E342K. RESULTS: We identified 1 mutated allele in at least 1 of 4 genes in 31 of 92 patients and 12 of 50 controls (P = 0.157). Mutations in SPINK1 and PRSS1 were most frequent. PRSS1 mutations were identified mainly in CPpatients (9.6% of CP vs 2.5% of ARP alleles, P = 0.094), whereas N34SSPINK1 mutation was present with comparable frequency in CP and ARP patients (7.7% vs 10.0%, P = 0.768). The frequency of mutations in CFTR alleles was similar to controls (4.9% vs 5%, P = 0.587). Overall frequency of AAT mutations was lower than in the controls. Family studies showed that defects in the examined genes did not always segregate with disease. CONCLUSIONS:PRSS1 defects seem to be causative for pancreatitis, whereas defects in SPINK1 are suggested to be associated with the disease. No association between CFTR mutations and pancreatitis was observed. The importance of AAT variants remains speculative.
Authors: Quin Y Liu; Maisam Abu-El-Haija; Sohail Z Husain; Bradley Barth; Melena Bellin; Douglas S Fishman; Steven D Freedman; Cheryl E Gariepy; Matthew J Giefer; Tanja Gonska; Melvin B Heyman; Ryan Himes; Tom K Lin; Asim Maqbool; Maria Mascarenhas; Brian A McFerron; Veronique D Morinville; Jaimie D Nathan; Chee Y Ooi; Emily R Perito; John F Pohl; Sue Rhee; Sarah J Schwarzenberg; Uzma Shah; David Troendle; Steven L Werlin; Michael Wilschanski; M Bridget Zimmerman; Mark E Lowe; Aliye Uc Journal: J Pediatr Gastroenterol Nutr Date: 2019-08 Impact factor: 2.839
Authors: Alexander Schneider; Jessica Larusch; Xiumei Sun; Amy Aloe; Janette Lamb; Robert Hawes; Peter Cotton; Randall E Brand; Michelle A Anderson; Mary E Money; Peter A Banks; Michele D Lewis; John Baillie; Stuart Sherman; James Disario; Frank R Burton; Timothy B Gardner; Stephen T Amann; Andres Gelrud; Ryan George; Matthew J Rockacy; Sirvart Kassabian; Jeremy Martinson; Adam Slivka; Dhiraj Yadav; Nevin Oruc; M Michael Barmada; Raymond Frizzell; David C Whitcomb Journal: Gastroenterology Date: 2010-10-25 Impact factor: 22.682
Authors: Matthew J Giefer; Mark E Lowe; Steven L Werlin; Bridget Zimmerman; Michael Wilschanski; David Troendle; Sarah Jane Schwarzenberg; John F Pohl; Joseph Palermo; Chee Y Ooi; Veronique D Morinville; Tom K Lin; Sohail Z Husain; Ryan Himes; Melvin B Heyman; Tanja Gonska; Cheryl E Gariepy; Steven D Freedman; Douglas S Fishman; Melena D Bellin; Bradley Barth; Maisam Abu-El-Haija; Aliye Uc Journal: J Pediatr Date: 2017-05-10 Impact factor: 4.406
Authors: Joseph J Palermo; Tom K Lin; Lindsey Hornung; C Alexander Valencia; Abhinav Mathur; Kimberly Jackson; Lin Fei; Maisam Abu-El-Haija Journal: Pancreas Date: 2016-10 Impact factor: 3.327
Authors: Sarah Jane Schwarzenberg; Melena Bellin; Sohail Z Husain; Monika Ahuja; Bradley Barth; Heather Davis; Peter R Durie; Douglas S Fishman; Steven D Freedman; Cheryl E Gariepy; Matthew J Giefer; Tanja Gonska; Melvin B Heyman; Ryan Himes; Soma Kumar; Veronique D Morinville; Mark E Lowe; Neil E Nuehring; Chee Y Ooi; John F Pohl; David Troendle; Steven L Werlin; Michael Wilschanski; Elizabeth Yen; Aliye Uc Journal: J Pediatr Date: 2014-12-30 Impact factor: 4.406
Authors: Soma Kumar; Chee Y Ooi; Steven Werlin; Maisam Abu-El-Haija; Bradley Barth; Melena D Bellin; Peter R Durie; Douglas S Fishman; Steven D Freedman; Cheryl Gariepy; Matthew J Giefer; Tanja Gonska; Melvin B Heyman; Ryan Himes; Sohail Z Husain; Tom K Lin; Mark E Lowe; Veronique Morinville; Joseph J Palermo; John F Pohl; Sarah Jane Schwarzenberg; David Troendle; Michael Wilschanski; M Bridget Zimmerman; Aliye Uc Journal: JAMA Pediatr Date: 2016-06-01 Impact factor: 16.193