title: A novel exon duplication of the cystic fibrosis transmembrane conductance regulator in a patient presenting with adult-onset recurrent pancreatitis.
abstract: Pancreatitis is a rare occurrence in patients with cystic fibrosis (CF) affecting 1.2% of all patients, but it can be the first presenting sign in approximately 15% of adults with pancreatic sufficiency and a milder CF phenotype. We report a case of a woman with recurrent pancreatitis who has one cystic fibrosis-causing mutation (G551D) and the first known description of a pathologic duplication of exon 19 of the CF transmembrane conductance regulator (CFTR). A 30-year-old white woman with 30 attacks of pancreatitis over a 5-year period starting at age 25 presented to the genetics department. She was found to have a mutation in the SPINK1 gene, IVS3+184T>A, and one cystic fibrosis-causing mutation (G551D) prompting full gene sequencing of the CFTR, revealing an additional duplication of exon 19. Sweat chloride testing was elevated at 97 and 106 mmol/L. Despite normal growth parameters and lung function, it is important to be aware of recurrent pancreatitis as a presenting sign of CF. Comprehensive CF gene analysis is necessary to detect a second CF-causing mutation that may put patients at risk for more severe symptoms of pancreatitis. There is a significant difference in the prevalence of heterozygote mutations between available testing methods.
authors.affiliation: Sections of Pulmonary Medicine, Nationwide Children's Hospital, Columbus, OH 43205, USA. Benjamin.Kopp@Nationwidechildrens.org
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Kopp
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Pastore
authors.forename: Amy C
authors.initials: AC
authors.lastname: Sturm
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Holtzlander
authors.forename: Judith A
authors.initials: JA
authors.lastname: Westman
mesh_terms: D000328:Adult; D017668:Age of Onset; D002352:Carrier Proteins / Q000235:genetics; D003550:Cystic Fibrosis / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D009154:Mutation; D050500:Pancreatitis, Chronic / Q000209:etiology / Q000235:genetics*; D012008:Recurrence; D056916:Segmental Duplications, Genomic; D014359:Trypsin Inhibitor, Kazal Pancreatic
chemical_list: C505032:CFTR protein, human; D002352:Carrier Proteins; C486642:SPINK1 protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014359:Trypsin Inhibitor, Kazal Pancreatic