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dc.contributor.authorMartin, P
dc.contributor.authorHeiskari, N
dc.contributor.authorZhou, J
dc.contributor.authorLeinonen, A
dc.contributor.authorTumelius, T
dc.contributor.authorHertz, J M
dc.contributor.authorBarker, D
dc.contributor.authorGregory, M
dc.contributor.authorAtkin, C
dc.contributor.authorStyrkarsdottir, U
dc.contributor.authorNeumann, H
dc.contributor.authorSpringate, J
dc.contributor.authorShows, T
dc.contributor.authorPettersson, E
dc.contributor.authorTryggvason, K
dc.date.accessioned2010-03-02T13:45:05Z
dc.date.available2010-03-02T13:45:05Z
dc.date.issued1998-12-01
dc.date.submitted2010-03-02
dc.identifier.citationJ. Am. Soc. Nephrol. 1998, 9(12):2291-301en
dc.identifier.issn1046-6673
dc.identifier.pmid9848783
dc.identifier.urihttp://hdl.handle.net/2336/93394
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractApproximately 85% of patients with Alport syndrome (hereditary nephritis) have been estimated to have mutations in the X chromosomal COL4A5 collagen gene; the remaining cases are autosomal with mutations in the COL4A3 or COL4A4 genes located on chromosome 2. In the present work, the promoter sequence and previously unknown intron sequences flanking exons 2 and 37 of COL4A5 were determined. Furthermore, intron sequences flanking the other 49 exons were expanded from 35 to 190 to facilitate mutation analysis of the gene. Using this information, all 51 exons and the promoter region were PCR-amplified and sequenced from DNA of 50 randomly chosen patients with suspected Alport syndrome. Mutations were found in 41 patients, giving a mutation detection rate of 82%. Retrospective analysis of clinical data revealed that two of the cases might be autosomal. Although it could not be determined whether the remaining seven cases (14%) were autosomal or X chromosome-linked, it is likely that some of them were autosomal. It is concluded that PCR amplification and direct DNA sequencing of the promoter and exons is currently the best procedure to detect mutations in COL4A5 in Alport syndrome.
dc.language.isoenen
dc.publisherAmerican Society of Nephrologyen
dc.relation.urlhttp://jasn.asnjournals.org/cgi/content/abstract/9/12/2291en
dc.subject.meshAmino Acid Substitutionen
dc.subject.meshBase Sequenceen
dc.subject.meshChromosomes, Human, Pair 2en
dc.subject.meshCollagenen
dc.subject.meshDNA Mutational Analysisen
dc.subject.meshExonsen
dc.subject.meshFemaleen
dc.subject.meshFrameshift Mutationen
dc.subject.meshGenetic Heterogeneityen
dc.subject.meshHumansen
dc.subject.meshIntronsen
dc.subject.meshMaleen
dc.subject.meshMolecular Sequence Dataen
dc.subject.meshMutation, Missenseen
dc.subject.meshNephritis, Hereditaryen
dc.subject.meshPoint Mutationen
dc.subject.meshPolymerase Chain Reactionen
dc.subject.meshPromoter Regions, Geneticen
dc.subject.meshProtein Isoformsen
dc.subject.meshRNA Splicingen
dc.subject.meshSequence Alignmenten
dc.subject.meshSequence Analysis, DNAen
dc.subject.meshSequence Deletionen
dc.subject.meshSequence Homology, Nucleic Aciden
dc.subject.meshX Chromosomeen
dc.titleHigh mutation detection rate in the COL4A5 collagen gene in suspected Alport syndrome using PCR and direct DNA sequencingen
dc.typeArticleen
dc.contributor.departmentBiocenter and Department of Biochemistry, University of Oulu, Finland.en
dc.identifier.journalJournal of the American Society of Nephrology : JASNen
html.description.abstractApproximately 85% of patients with Alport syndrome (hereditary nephritis) have been estimated to have mutations in the X chromosomal COL4A5 collagen gene; the remaining cases are autosomal with mutations in the COL4A3 or COL4A4 genes located on chromosome 2. In the present work, the promoter sequence and previously unknown intron sequences flanking exons 2 and 37 of COL4A5 were determined. Furthermore, intron sequences flanking the other 49 exons were expanded from 35 to 190 to facilitate mutation analysis of the gene. Using this information, all 51 exons and the promoter region were PCR-amplified and sequenced from DNA of 50 randomly chosen patients with suspected Alport syndrome. Mutations were found in 41 patients, giving a mutation detection rate of 82%. Retrospective analysis of clinical data revealed that two of the cases might be autosomal. Although it could not be determined whether the remaining seven cases (14%) were autosomal or X chromosome-linked, it is likely that some of them were autosomal. It is concluded that PCR amplification and direct DNA sequencing of the promoter and exons is currently the best procedure to detect mutations in COL4A5 in Alport syndrome.


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