Low Penetrance Pancreatitis Phenotype in a Venezuelan Kindred with a PRSS1 R122H Mutation

  • Sheila Solomon Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh. Pittsburgh, PA, USA
  • Andres Gelrud Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh. Pittsburgh, PA, USA
  • David C Whitcomb Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh. Pittsburgh, PA, USA
Keywords: Hereditary pancreatitis, Pancreatitis, Chronic, PRSS1 protein, human


Context Hereditary pancreatitis is typically caused by the PRSS1 R122H or N29I mutations resulting in high penetrance (about 80%) autosomal dominant disorder that is usually reported in North America, Northern Europe and Northeast Asia, but not South America, Africa or India. Case report Here we report a kindred from Venezuela, South America with the PRSS1 R122H variant. Only the proband, an 11-year old boy with severe chronic pancreatitis, and a maternal grandmother with pancreatitis at age 60 years (confirmed PRSS1 R122H), are symptomatic. Conclusions Issues of mutation prevalence, non-penetrance, and disease recognition in various countries are discussed.

Image: Pedigree of a Venezuelan kindred.


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Whitcomb DC, Gorry MC, Preston RA, Furey W, Sossenheimer MJ, Ulrich CD, et al. Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene. Nature Genetics. 1996;14(2):141-5. [PMID: 8841182]

Solomon S, Whitcomb DC, LaRusch J.Related Hereditary Pancreatitis. In: Pagon RA, Bird TD, Dolan CR, Stephens K, editors. GeneReviews. Seattle (WA)1993.

Solomon S, Whitcomb DC. Genetics of Pancreatitis: An Update for Clinicians and Genetic Counselors. Current gastroenterology reports. 2012 Feb 8;14(2):112-7. [PMID: 22314809]

Nishimori I, Kamakura M, Fujikawa-Adachi K, Morita M, Onishi S, Yokoyama K, et al. Mutations in exon 2 and 3 of the cationic trypsinogen gene in japanese families with hereditary pancreatitis. Gut. 1999;44:259-63. [PMID]

Otsuki M, Nishimori I, Hayakawa T, Hirota M, Ogawa M, Shimosegawa T. Hereditary pancreatitis: clinical characteristics and diagnostic criteria in Japan. Pancreas. 2004 Mar;28(2):200-6. [PMID: 15028953]

Lee YJ, Kim KM, Choi JH, Lee BH, Kim GH, Yoo HW. High incidence of PRSS1 and SPINK1 mutations in Korean children with acute recurrent and chronic pancreatitis. Journal of pediatric gastroenterology and nutrition. 2011 Apr;52(4):478-81. [PMID: 21415673]

Chang YT, Wei SC, L PC, Tien YW, Jan IS, Su YN, et al. Association and differential role of PRSS1 and SPINK1 mutation in early-onset and late-onset idiopathic chronic pancreatitis in Chinese subjects. Gut. 2009 Jun;58(6):885. [PMID: 19433603]

Liu QC, Gao F, Ou QS, Zhuang ZH, Lin SR, Yang B, et al. Novel mutation and polymorphism of PRSS1 gene in the Chinese patients with hereditary pancreatitis and chronic pancreatitis. Chin Med J (Engl). 2008 Jan 20;121(2):108-11. [PMID: 18272034]

Chua KH, Puah SM, Chew CH, Wong CH, Goh KL. Interaction between a novel intronic IVS3+172 variant and N29I mutation in PRSS1 gene is associated with pancreatitis in a Malaysian Chinese family. Pancreatology : official journal of the International Association of Pancreatology. 2011;11(4):441-4. [PMID: 21952138]

Siegel S, de Aretxabala X, Burgos L. [Hereditary chronic pancreatitis. Report of a case]. Rev Med Chil. 1995 May;122(5):542-5. [PMID: 7724895]

Bernardino AL, Guarita DR, Mott CB, Pedroso MR, Machado MC, Laudanna AA, et al. CFTR, PRSS1 and SPINK1 mutations in the development of pancreatitis in Brazilian patients. JOP. 2003 Sep;4(5):169-77. [PMID: 14526128]

da Costa MZ, Guarita DR, Ono-Nita SK, Paranagua-Vezozzo DC, Felga GE, Pedroso MR, et al. Genetic risk for alcoholic chronic pancreatitis. Int J Environ Res Public Health. 2011 Jul;8(7):2747-57. [PMID: 21845156]

Sanchez-Ramirez CA, Flores-Martinez SE, Garcia-Zapien AG, Montero-Cruz SA, Larrosa-Haro A, Sanchez-Corona J. Screening of R122H and N29I Mutations in the PRSS1 Gene and N34S Mutation in the SPINK1 Gene in Mexican Pediatric Patients With Acute and Recurrent Pancreatitis. Pancreas. 2012 Jul;41(5):707-11. [PMID: 22699143]

Chandak GR, Idris MM, Reddy DN, Mani KR, Bhaskar S, Rao GV, et al. Absence of PRSS1 mutations and association of SPINK1 trypsin inhibitor mutations in hereditary and non-hereditary chronic pancreatitis. Gut. 2004 May;53(5):723-8. [PMID: 15082592]

Bhatia E, Choudhuri G, Sikora SS, Landt O, Kage A, Becker M, et al. Tropical calcific pancreatitis: strong association with SPINK1 trypsin inhibitor mutations. Gastroenterology. 2002;123(4):1020-5. [PMID]

Chen JM, Ferec C. Gene conversion-like missense mutations in the human cationic trypsinogen gene and insights into the molecular evolution of the human trypsinogen family. Mol Genet Metab. 2000;71(3):463-9. [PMID]

Masson E, Le Marechal C, Chandak GR, Lamoril J, Bezieau S, Mahurkar S, et al. Trypsinogen copy number mutations in patients with idiopathic chronic pancreatitis. Clin Gastroenterol Hepatol. 2008 Jan;6(1):82-8. [PMID: 18063422]

Larusch J, Barmada MM, Solomon S, Whitcomb DC. Whole exome sequencing identifies multiple, complex etiologies in an idiopathic hereditary pancreatitis kindred. JOP : Journal of the pancreas. 2012;13(3):258-62. [PMID: 22572128]

Bertin C, Pelletier AL, Vullierme MP, Bienvenu T, Rebours V, Hentic O, et al. Pancreas Divisum Is Not a Cause of Pancreatitis by Itself But Acts as a Partner of Genetic Mutations. The American journal of gastroenterology. 2011 Dec 13;107(2):31-7. [PMID: 22158025]

Cavestro GM, Zuppardo RA, Bertolini S, Sereni G, Frulloni L, Okolicsanyi S, et al. Connections between genetics and clinical data: Role of MCP-1, CFTR, and SPINK-1 in the setting of acute, acute recurrent, and chronic pancreatitis. Am J Gastroenterol. 2010 Jan;105(1):199-206. [PMID: 19844201]

Garg PK, Khajuria R, Kabra M, Shastri SS. Association of SPINK1 gene mutation and CFTR gene polymorphisms in patients with pancreas divisum presenting with idiopathic pancreatitis. Journal of clinical gastroenterology. 2009 Oct;43(9):848-52. [PMID: 19593166]

Gelrud A, Sheth S, Banerjee S, Weed D, Shea J, Chuttani R, et al. Analysis of cystic fibrosis gener product (CFTR) function in patients with pancreas divisum and recurrent acute pancreatitis. The American journal of gastroenterology. 2004 Aug;99(8):1557-62. [PMID: 15307877]

Amann ST, Gates LK, Aston CE, Pandya A, Whitcomb DC. Expression and penetrance of the hereditary pancreatitis phenotype in monozygotic twins. Gut. 2001;48(4):542-7. [PMID]

Khalid A, Finkelstein S, Thompson B, Kelly L, Hanck C, Godfrey TE, et al. A 93 year old man with the PRSS1 R122H mutation, low SPINK1 expression, and no pancreatitis: insights into phenotypic non-penetrance. Gut. 2006 May;55(5):728-31. [PMID: 16354799]

Pedigree of a Venezuelan kindred
How to Cite
SolomonS., GelrudA., & WhitcombD. (2013). Low Penetrance Pancreatitis Phenotype in a Venezuelan Kindred with a PRSS1 R122H Mutation. JOP. Journal of the Pancreas, 14(2), 187-189. https://doi.org/10.6092/1590-8577/1276