Phenotypic Variability of the Homozygous IVS3+2T>C Mutation in the Serine Protease Inhibitor Kazal Type 1 (SPINK1) Gene in Patients with Chronic Pancreatitis

• Published in: The Tohoku Journal of Experimental Medicine Vol. 221; no. 3; pp. 197 - 201
• Main Authors: Ota, Yuji, Masamune, Atsushi, Inui, Kazuo, Kume, Kiyoshi, Shimosegawa, Tooru, Kikuyama, Masataka
• Format: Journal Article
• Language: English
• Published: Japan Tohoku University Medical Press 01.07.2010
• Subjects: Adult; Aged; Alcoholics; Exons; Female; Genetic Diseases, Inborn - genetics; Glycogen Storage Disease Type IIb - genetics; Homozygote; Humans; Introns; Male; mutation; Mutation - genetics; Myopathy, Central Core - genetics; Optic Atrophy, Autosomal Dominant - genetics; pancreatitis; Pancreatitis - genetics; Pancreatitis, Alcoholic - genetics; Pancreatitis, Chronic - genetics; polymorphism; Serine Proteases; Serine Proteinase Inhibitors - genetics; trypsin; Trypsin - genetics; Trypsin Inhibitor, Kazal Pancreatic - genetics; trypsinogen; Urea Cycle Disorders, Inborn
• ISSN: 0040-8727; 1349-3329
• DOI: 10.1620/tjem.221.197

Chronic pancreatitis (CP) is a progressive inflammatory disease that eventually results in the impairment of exocrine and endocrine functions of the pancreas. Recent studies have shown an association between mutations in the serine protease inhibitor Kazal type 1 (SPINK1) gene and CP. SPINK1 provides the first line of defense against prematurely activated trypsinogen by physically blocking the active site of trypsin. The IVS3+2T>C (c.194+2T>C) mutation is a loss-of-function splicing mutation; it affects the consensus splicing donor site in intron 3 and may cause the skipping of the entire exon 3, where the trypsin-binding site is located. We report here three CP patients carrying this mutation in a homozygous form, with no noticeable family history of pancreatitis. The first patient is a 25-year-old male with juvenile-onset idiopathic CP. He suffered from repeated attacks of pancreatitis since 5 years old and underwent pancreatico-jejunostomy. He complained of epigastralgia, and was diagnosed as obstructive pancreatitis in the area of the accessory pancreatic duct. The second patient is a 75-year-old male with alcoholic CP. He did not have apparent attacks of pancreatitis, but had numerous calcifications throughout the pancreas and confirmed exocrine failure and diabetes mellitus. The last patient is a 44-year-old female with late-onset idiopathic CP. She suffered from repeated attacks of pancreatitis since 32 years old. She had numerous stones in the main pancreatic duct in the pancreas head and confirmed exocrine failure. The clinical courses of these patients are apparently different, indicating the phenotypic variability of the SPINK1 IVS3+2T>C mutation-associated CP.