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Hereditary pancreatitis caused by triplication of the trypsinogen locus

Abstract

Hereditary pancreatitis has been reported to be caused by 'gain-of-function' missense mutations in the cationic trypsinogen gene (PRSS1). Here we report the triplication of a 605-kb segment containing the PRSS1 gene on chromosome 7 in five families with hereditary pancreatitis. This triplication, which seems to result in a gain of trypsin through a gene dosage effect, represents a previously unknown molecular mechanism causing hereditary pancreatitis.

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Figure 1: Detection of trypsinogen locus triplication.
Figure 2: Trypsinogen locus triplication in five families.

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Acknowledgements

We are grateful to D.N. Cooper for critically reading this manuscript. We thank P.J. Guillausseau (Hôpital Lariboisiere), A. Morali (Hôpital d'Enfants) and A. Munnich (Hôpital Necker-Enfants Malades) for contribution of samples. E.M. is a PhD student supported by the Programme Hospitalier de Recherche Clinique (grant PHRC R 08-04 to C.F.). J.M.C. is a visiting Professor of Genetics supported by the Ministère de la Jeunesse, de l'Éducation Nationale et de la Recherche, France. This work was supported by the INSERM, the 'Partenariats Institutions Citoyens pour la Recherche et l'Innovation' project and the Association des Pancréatites Chroniques Héréditaires.

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Authors and Affiliations

Authors

Contributions

C.L.M. and E.M. performed the research, analyzed the data and helped in writing the manuscript. J.-M.C conceived the study, analyzed the data and drafted the manuscript. F.M. performed the FISH analysis. P.R. and P.L. collected samples and evaluated patients. C.F. supervised the overall project, analyzed the data and drafted the manuscript. All authors approved the manuscript.

Corresponding author

Correspondence to Jian-Min Chen.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

qHPLC analysis of the PRSS1 gene. (PDF 610 kb)

Supplementary Fig. 2

Screen shot of the UCSC genome browser at the 7q34 locus. (PDF 534 kb)

Supplementary Fig. 3

Genotyping of the microsatellite marker rs3222967. (PDF 304 kb)

Supplementary Methods (PDF 439 kb)

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Le Maréchal, C., Masson, E., Chen, JM. et al. Hereditary pancreatitis caused by triplication of the trypsinogen locus. Nat Genet 38, 1372–1374 (2006). https://doi.org/10.1038/ng1904

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