https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 Mutations in ionotropic AMPA receptor 3 alter channel properties and are associated with moderate cognitive impairment in humans https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:3341 Sat 24 Mar 2018 07:22:35 AEDT ]]> Bioinformatics-based identification of expanded repeats:a non-reference intronic pentamer expansion in RFC1 causes CANVAS https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36658 exp] in the gene encoding Replication Factor C1 (RFC1). This motif, not reported in the reference sequence, localized to an Alu element and replaced the reference (AAAAG)11 short tandem repeat. Genetic analyses confirmed the pathogenic expansion in 18 of 22 CANVAS-affected families and identified a core ancestral haplotype, estimated to have arisen in Europe more than twenty-five thousand years ago. WGS of the four RFC1-negative CANVAS-affected families identified plausible variants in three, with genomic re-diagnosis of SCA3, spastic ataxia of the Charlevoix-Saguenay type, and SCA45. This study identified the genetic basis of CANVAS and demonstrated that these improved bioinformatics tools increase the diagnostic utility of WGS to determine the genetic basis of a heterogeneous group of clinically overlapping neurogenetic disorders.]]> Mon 22 Jun 2020 15:22:42 AEST ]]>