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dc.contributor.authorKoptides, Michaelen
dc.contributor.authorMean, R.en
dc.contributor.authorDemetriou, Kyproulaen
dc.contributor.authorPierides, Alkis M.en
dc.contributor.authorConstantinou-Deltas, Constantinos D.en
dc.creatorKoptides, Michaelen
dc.creatorMean, R.en
dc.creatorDemetriou, Kyproulaen
dc.creatorPierides, Alkis M.en
dc.creatorConstantinou-Deltas, Constantinos D.en
dc.date.accessioned2019-11-04T12:52:12Z
dc.date.available2019-11-04T12:52:12Z
dc.date.issued2000
dc.identifier.urihttp://gnosis.library.ucy.ac.cy/handle/7/53192
dc.description.abstractPolycystic kidney disease (ADPKD) is a condition with an autosomal dominant mode of inheritance and adult onset. Two forms of the disease, ADPKD1 and ADPKD2, caused by mutations in PKD1 and PKD2, respectively, are very similar, except that ADPKD1 patients run a more severe course. At the cellular level, ADPKD1 was first shown to be recessive, since somatic second hits are perhaps necessary for cyst formation. The near identical phenotype had suggested that ADPKD1 and ADPKD2 might have a similar pathogenesis and that the two gene products, polycystins 1 and 2, are part of a common developmental pathway. Work in transgenic mice showed that somatic loss of Pkd2 expression is necessary for renal cyst formation, and recently we showed that somatic mutations inactivating the inherited healthy allele were present in 9 of 23 cysts from a human ADPKD2 kidney, supporting a two-hit loss-of-function model for ADPKD2 cystogenesis. Here, we provide the first direct genetic evidence that polycystins 1 and 2 do interact, perhaps as part of a larger complex. In cystic DNA from a kidney of an ADPKD1 patient, we showed somatic mutations not only in the PKD1 gene of certain cysts, but also in the PKD2 gene of others, generating a trans-heterozygous state with mutations in both genes. One mutation in PKD1 is of germinal nature and the mutation in the PKD2 gene is of somatic nature. The implications of such a situation are enormous, not only for ADPKD, but also for many other conditions with phenotypic heterogeneity and age-dependent penetrance.en
dc.sourceHuman molecular geneticsen
dc.source.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-0034639655&partnerID=40&md5=8b9944fef8d2b2c6be4604cd30600a7b
dc.subjectarticleen
dc.subjecthumanen
dc.subjectHumansen
dc.subjectfemaleen
dc.subjectpriority journalen
dc.subjectclinical articleen
dc.subjectkidney polycystic diseaseen
dc.subjectdisease courseen
dc.subjectmaleen
dc.subjectpathogenesisen
dc.subjectLoss of Heterozygosityen
dc.subjectphenotypeen
dc.subjectgene expressionen
dc.subjectBase Sequenceen
dc.subjectgene mutationen
dc.subjectMolecular Sequence Dataen
dc.subjectPolymerase Chain Reactionen
dc.subjectMembrane Proteinsen
dc.subjectDNA Mutational Analysisen
dc.subjectHeterozygoteen
dc.subjectProteinsen
dc.subjectPedigreeen
dc.subjectAmino Acid Sequenceen
dc.subjectPolycystic Kidney, Autosomal Dominanten
dc.subjectautosomal dominant inheritanceen
dc.subjectpolycystinen
dc.subjectPolymorphism, Single-Stranded Conformationalen
dc.subjectTRPP Cation Channelsen
dc.subjectonset ageen
dc.subjecttransgenic mouseen
dc.titleGenetic evidence for a trans-heterozygous model for cystogenesis in autosomal dominant polycystic kidney diseaseen
dc.typeinfo:eu-repo/semantics/article
dc.description.volume9
dc.description.startingpage447
dc.description.endingpage452
dc.author.facultyΣχολή Θετικών και Εφαρμοσμένων Επιστημών / Faculty of Pure and Applied Sciences
dc.author.departmentΤμήμα Βιολογικών Επιστημών / Department of Biological Sciences
dc.type.uhtypeArticleen
dc.description.notes<p>Cited By :74</p>en
dc.source.abbreviationHum.Mol.Genet.en
dc.contributor.orcidConstantinou-Deltas, Constantinos D. [0000-0001-5549-9169]
dc.gnosis.orcid0000-0001-5549-9169


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