Heterogeneity in hereditary pancreatitis

Majed J. Dasouki, Joy Cogan, Marshall L. Summar, Wallace Neblitt, Tatiana Foroud, Dan Koller, John A. Phillips

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


Hereditary pancreatitis (HP) is the most common form of chronic relapsing pancreatitis in childhood, and may account for ~25% of adult cases with chronic idiopathic pancreatitis. Recently, an arginine-histidine (R117H) mutation within the cationic trypsinogen gene was found in 5/5 families studied with HP. In this study we report on the results of linkage and direct mutational analysis for the common R117H mutation examined in 8 nonrelated families with hereditary pancreatitis. Two-point linkage analysis with the 7q35 marker D7S676, done initially in 4 families, yielded lod scores that were positive in 2, negative in one, and weakly positive in one. Direct mutational analysis of exon 3 of the cationic trypsinogen gene in 6 families showed that all symptomatic individuals tested were heterozygous for the R117H mutation. Also, several asymptomatic but at-risk relatives were found to be heterozygous for this mutation. Affected individuals in the remaining 2 families did not have the mutation. Radiation hybrid mapping using the Genebridge 4 panel assigned the trypsinogen gene to chromosome region 7q35, 2.9 cR distal to ETS WI-9353 and 3.8 cR proximal the dinucleotide repeat marker D7S676. The negative linkage and absence of the trypsinogen mutation in 2/8 families suggest locus heterogeneity in HP. Analysis of the R117H mutation is useful in identifying presymptomatic 'at-risk' relatives and in genetic counseling. Also, it can be useful in identifying children and adults with isolated chronic idiopathic pancreatitis.

Original languageEnglish (US)
Pages (from-to)47-53
Number of pages7
JournalAmerican journal of medical genetics
Issue number1
StatePublished - Apr 28 1998


  • Centiray
  • Endoscopic retrograde cholangiopancreatography
  • Expressed tagged sequence
  • Hereditary pancreatitis
  • Logarithm of odds
  • Polymerase chain reaction
  • T-cell receptor β polypeptide
  • Theta (recombination fraction)

ASJC Scopus subject areas

  • Genetics(clinical)

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