Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/10546
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dc.contributor.authorBerkovic, Samuel Fen
dc.contributor.authorDibbens, Leanne Men
dc.contributor.authorOshlack, Aliciaen
dc.contributor.authorSilver, Jeremy Den
dc.contributor.authorKaterelos, Marinaen
dc.contributor.authorVears, Danya Fen
dc.contributor.authorLüllmann-Rauch, Renateen
dc.contributor.authorBlanz, Judithen
dc.contributor.authorZhang, Ke Weien
dc.contributor.authorStankovich, Jimen
dc.contributor.authorKalnins, Renate Men
dc.contributor.authorDowling, John Pen
dc.contributor.authorAndermann, Evaen
dc.contributor.authorAndermann, Fredericken
dc.contributor.authorFaldini, Enricoen
dc.contributor.authorD'Hooge, Rudien
dc.contributor.authorVadlamudi, Lataen
dc.contributor.authorMacdonell, Richard A Len
dc.contributor.authorHodgson, Bree Len
dc.contributor.authorBayly, Marta Aen
dc.contributor.authorSavige, Judy Aen
dc.contributor.authorMulley, John Cen
dc.contributor.authorSmyth, Gordon Ken
dc.contributor.authorPower, David Anthonyen
dc.contributor.authorSaftig, Paulen
dc.contributor.authorBahlo, Melanieen
dc.date.accessioned2015-05-16T00:02:26Z
dc.date.available2015-05-16T00:02:26Z
dc.date.issued2008-02-28en
dc.identifier.citationAmerican Journal of Human Genetics 2008; 82(3): 673-84en
dc.identifier.govdoc18308289en
dc.identifier.otherPUBMEDen
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/10546en
dc.description.abstractAction myoclonus-renal failure syndrome (AMRF) is an autosomal-recessive disorder with the remarkable combination of focal glomerulosclerosis, frequently with glomerular collapse, and progressive myoclonus epilepsy associated with storage material in the brain. Here, we employed a novel combination of molecular strategies to find the responsible gene and show its effects in an animal model. Utilizing only three unrelated affected individuals and their relatives, we used homozygosity mapping with single-nucleotide polymorphism chips to localize AMRF. We then used microarray-expression analysis to prioritize candidates prior to sequencing. The disorder was mapped to 4q13-21, and microarray-expression analysis identified SCARB2/Limp2, which encodes a lysosomal-membrane protein, as the likely candidate. Mutations in SCARB2/Limp2 were found in all three families used for mapping and subsequently confirmed in two other unrelated AMRF families. The mutations were associated with lack of SCARB2 protein. Reanalysis of an existing Limp2 knockout mouse showed intracellular inclusions in cerebral and cerebellar cortex, and the kidneys showed subtle glomerular changes. This study highlights that recessive genes can be identified with a very small number of subjects. The ancestral lysosomal-membrane protein SCARB2/LIMP-2 is responsible for AMRF. The heterogeneous pathology in the kidney and brain suggests that SCARB2/Limp2 has pleiotropic effects that may be relevant to understanding the pathogenesis of other forms of glomerulosclerosis or collapse and myoclonic epilepsies.en
dc.language.isoenen
dc.subject.otherAnimalsen
dc.subject.otherCerebellar Cortex.pathologyen
dc.subject.otherChromosome Mappingen
dc.subject.otherChromosomes, Human, Pair 4.geneticsen
dc.subject.otherGene Expressionen
dc.subject.otherGenes, Recessiveen
dc.subject.otherGenetic Linkageen
dc.subject.otherGenotypeen
dc.subject.otherGlomerulonephritis.genetics.pathologyen
dc.subject.otherHumansen
dc.subject.otherLysosome-Associated Membrane Glycoproteins.geneticsen
dc.subject.otherMiceen
dc.subject.otherMice, Knockouten
dc.subject.otherMyoclonic Epilepsies, Progressive.genetics.pathologyen
dc.subject.otherOligonucleotide Array Sequence Analysisen
dc.subject.otherReceptors, Scavenger.geneticsen
dc.titleArray-based gene discovery with three unrelated subjects shows SCARB2/LIMP-2 deficiency causes myoclonus epilepsy and glomerulosclerosis.en
dc.typeJournal Articleen
dc.identifier.journaltitleAmerican journal of human geneticsen
dc.identifier.affiliationDepartment of Medicine, Austin Health and Northern Health, Heidelberg, Victoria 3081, Australiaen
dc.identifier.doi10.1016/j.ajhg.2007.12.019en
dc.description.pages673-84en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/18308289en
dc.type.austinJournal Articleen
local.name.researcherBerkovic, Samuel F
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.languageiso639-1en-
item.openairetypeJournal Article-
crisitem.author.deptEpilepsy Research Centre-
crisitem.author.deptNeurology-
crisitem.author.deptInstitute for Breathing and Sleep-
crisitem.author.deptNeurology-
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