Abstract
Mutations in PRKCSH, encoding the β-subunit of glucosidase II, an N-linked glycan-processing enzyme in the endoplasmic reticulum (ER), cause autosomal dominant polycystic liver disease. We found that mutations in SEC63, encoding a component of the protein translocation machinery in the ER, also cause this disease. These findings are suggestive of a role for cotranslational protein-processing pathways in maintaining epithelial luminal structure and implicate noncilial ER proteins in human polycystic disease.
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Acknowledgements
We thank the affected individuals and family members for their participation; K. Cornwell and P. Urban for help with recruiting study subjects; and R. Torra, X.M. Lens, M. Ott and Y. Pei for referring study subjects. The Keck Biotechnology Resource at Yale provided automated genotyping services and the Mayo Clinic General Clinical Research Center assisted with evaluations of study subjects. P.T, E.T, H.K. and K.H. received financial support from Mary and Georg C. Ehrnrooth Foundation. This work was supported by the US National Institutes of Health (S.S. and V.E.T.). S.S. is a member of the Yale Digestive Diseases Research Core Center; S.D., L.F, X.T., T.O, A.L., Y.C. and S.S. are members of the Yale Center for the Study of Polycystic Kidney Disease.
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Davila, S., Furu, L., Gharavi, A. et al. Mutations in SEC63 cause autosomal dominant polycystic liver disease. Nat Genet 36, 575–577 (2004). https://doi.org/10.1038/ng1357
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DOI: https://doi.org/10.1038/ng1357
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