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dc.contributor.authorEsposito, Teresa
dc.contributor.authorLea, Rod A
dc.contributor.authorMaher, Bridget H
dc.contributor.authorMoses, Dianne
dc.contributor.authorCox, Hannah C
dc.contributor.authorMagliocca, Sara
dc.contributor.authorAngius, Andrea
dc.contributor.authorNyholt, Dale R
dc.contributor.authorTitus, Thomas
dc.contributor.authorKay, Troy
dc.contributor.authorGray, Nicholas A
dc.contributor.authorRastaldi, Maria P
dc.contributor.authorParnham, Alan
dc.contributor.authorGianfrancesco, Fernando
dc.contributor.authorGriffiths, Lyn R
dc.date.accessioned2017-05-03T13:13:58Z
dc.date.available2017-05-03T13:13:58Z
dc.date.issued2013
dc.date.modified2014-06-17T04:52:23Z
dc.identifier.issn0964-6906
dc.identifier.doi10.1093/hmg/ddt215
dc.identifier.urihttp://hdl.handle.net/10072/60448
dc.description.abstractFocal segmental glomerulosclerosis (FSGS) is the consequence of a disease process that attacks the kidney's filtering system, causing serious scarring. More than half of FSGS patients develop chronic kidney failure within 10 years, ultimately requiring dialysis or renal transplantation. There are currently several genes known to cause the hereditary forms of FSGS (ACTN4, TRPC6, CD2AP, INF2, MYO1E and NPHS2). This study involves a large, unique, multigenerational Australian pedigree in which FSGS co-segregates with progressive heart block with apparent X-linked recessive inheritance. Through a classical combined approach of linkage and haplotype analysis, we identified a 21.19 cM interval implicated on the X chromosome. We then used a whole exome sequencing approach to identify two mutated genes, NXF5 and ALG13, which are located within this linkage interval. The two mutations NXF5-R113W and ALG13-T141L segregated perfectly with the disease phenotype in the pedigree and were not found in a large healthy control cohort. Analysis using bioinformatics tools predicted the R113W mutation in the NXF5 gene to be deleterious and cellular studies support a role in the stability and localization of the protein suggesting a causative role of this mutation in these co-morbid disorders. Further studies are now required to determine the functional consequence of these novel mutations to development of FSGS and heart block in this pedigree and to determine whether these mutations have implications for more common forms of these diseases in the general population.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherOxford University Press
dc.publisher.placeUnited Kingdom
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom3654
dc.relation.ispartofpageto3666
dc.relation.ispartofissue18
dc.relation.ispartofjournalHuman Molecular Genetics
dc.relation.ispartofvolume22
dc.rights.retentionY
dc.subject.fieldofresearchMedical and Health Sciences not elsewhere classified
dc.subject.fieldofresearchBiological Sciences not elsewhere classified
dc.subject.fieldofresearchBiological Sciences
dc.subject.fieldofresearchMedical and Health Sciences
dc.subject.fieldofresearchcode119999
dc.subject.fieldofresearchcode069999
dc.subject.fieldofresearchcode06
dc.subject.fieldofresearchcode11
dc.titleUnique X-linked familial FSGS with co-segregating heart block disorder is associated with a mutation in the NXF5 gene
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.hasfulltextNo Full Text
gro.griffith.authorGriffiths, Lyn
gro.griffith.authorLea, Rodney A.
gro.griffith.authorMoses, Dianne
gro.griffith.authorCox, Hannah
gro.griffith.authorMaher, Bridget
gro.griffith.authorNyholt, Dale R.


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