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dc.contributor.authorPei, Y
dc.contributor.authorLan, Z
dc.contributor.authorWang, K
dc.contributor.authorGarcía González , Miguel Ángel
dc.contributor.authorHe, N
dc.contributor.authorDicks, E
dc.contributor.authorParfrey, P
dc.contributor.authorGermino, G
dc.contributor.authorWatnick, T
dc.date.accessioned2017-06-07T07:33:13Z
dc.date.available2017-06-07T07:33:13Z
dc.date.issued2012
dc.identifier.issn0085-2538
dc.identifier.urihttp://hdl.handle.net/20.500.11940/7857
dc.description.abstractMutations of PKD1 and PKD2 account for most cases of autosomal dominant polycystic kidney disease (ADPKD). Compared with PKD2, patients with PKD1 typically have more severe renal disease. Here, we report a follow-up study of a unique multigeneration family with bilineal ADPKD (NFL10) in which a PKD1 disease haplotype and a PKD2 (L736X) mutation co-segregated with 18 and 14 affected individuals, respectively. In our updated genotype-phenotype analysis of the family, we found that PKD1-affected individuals had uniformly mild renal disease similar to the PKD2-affected individuals. By sequencing all the exons and splice junctions of PKD1, we identified two missense mutations (Y528C and R1942H) from a PKD1-affected individual. Although both variants were predicted to be damaging to the mutant protein, only Y528C co-segregated with all of the PKD1-affected individuals in NFL10. Studies in MDCK cells stably expressing wild-type and mutant forms of PKD found that cell lines expressing the Y528C variant formed cysts in culture and displayed increased rates of growth and apoptosis. Thus, Y528C functions as a hypomorphic PKD1 allele. These findings have important implications for pathogenic mechanisms and molecular diagnostics of ADPKD.
dc.language.isoeng
dc.titleA missense mutation in PKD1 attenuates the severity of renal disease
dc.typeArtigoes
dc.authorsophosPei, Y
dc.authorsophosLan, Z
dc.authorsophosWang, K
dc.authorsophosGarcia-Gonzalez, M
dc.authorsophosHe, N
dc.authorsophosDicks, E
dc.authorsophosParfrey, P
dc.authorsophosGermino, G
dc.authorsophosWatnick, T
dc.identifier.doi10.1038/ki.2011.370
dc.identifier.isiWOS:000299850400012
dc.identifier.pmid22031115
dc.identifier.sophos7852
dc.issue.number4
dc.journal.titleKIDNEY INTERNATIONAL
dc.organizationServizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::EOXI de Santiago - Complexo Hospitalario Universitario de Santiago::Nefroloxía
dc.organizationServizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::EOXI de Santiago::IDIS.- Instituto de investigaciones sanitarias de Santiago
dc.page.initial412
dc.page.final417
dc.relation.publisherversionhttp://www.kidney-international.org/article/S008525381555312X/pdfes
dc.rights.accessRightsopenAccess
dc.typesophosArtículo Original
dc.volume.number81 (4)


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