Abstract
Hereditary pancreatitis (HP) is the second most common cause of chronic childhood pancreatitis in the United States. Mutations in the cationic trypsinogen gene on chromosome 7 are known to cause HP. We identified four families in West Virginia with symptoms consistent with HP. To determine whether members of these families had defects in the trypsinogen gene, we tested for linkage between the HP gene and simple tandem repeat markers on chromosome 7q and screened for a specific mutation in the cationic trypsinogen gene. Two-point linkage analysis indicated that the disease gene is closely linked to three 7q markers (D7S661, D7S2511, and D7S1805). Restriction fragment length polymorphism analysis showed that all clinically affected members and nonpenetrant carriers from the four families carried a G to A mutation in the third exon of the trypsinogen gene. These findings indicate that this mutation is the cause of HP in the families in our study. The observation that most individuals who carry the mutation have symptoms of HP is consistent with the high but incomplete penetrance of the trait. The presence of a single mutation and a common linked haplotype indicates that the defective allele arose in an ancestor common to all four families.
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Abbreviations
- HP:
-
hereditary pancreatitis
- LOD:
-
logarithm of the odds
- STR:
-
simple tandem repeat
- cM:
-
centiMorgan
- RFLP:
-
restriction fragment length polymorphism
- PCR:
-
polymerase chain reaction
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Acknowledgements
The authors thank David C. Whitcomb and Elizabeth Bryda for critical review of this manuscript and Joel Napenas for technical support.
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Funding for this project was provided by the MU DNA Core facility.
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Elitsur, Y., Chertow, B., Jewell, R. et al. Identification of a Hereditary Pancreatitis Mutation in Four West Virginia Families. Pediatr Res 44, 927–930 (1998). https://doi.org/10.1203/00006450-199812000-00017
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DOI: https://doi.org/10.1203/00006450-199812000-00017
