https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 Computer face-matching technology using two-dimensional photographs accurately matches the facial gestalt of unrelated individuals with the same syndromic form of intellectual disability https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:31227 Wed 11 Apr 2018 14:09:18 AEST ]]> A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:7942 Sat 24 Mar 2018 08:34:59 AEDT ]]> Hybridisation-based resequencing of 17 X-linked intellectual disability genes in 135 patients reveals novel mutations in ATRX, SLC6A8 and PQBP1 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14330 90 different genes have been identified. In this study, we used a custom-made sequencing array based on the Affymetrix 50k platform for mutation screening in 17 known XLID genes in patients from 135 families and found eight single-nucleotide changes that were absent in controls. For four mutations affecting ATRX (p.1761M>T), PQBP1 (p.155R>X) and SLC6A8 (p.390P>L and p.477S>L), we provide evidence for a functional involvement of these changes in the aetiology of intellectual disability.]]> Sat 24 Mar 2018 08:26:21 AEDT ]]> Identification and characterization of two novel JARID1C mutations: suggestion of an emerging genotype-phenotype correlation https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:10419 A) in a published family with nonsyndromic MR, MRX13. This change occurs in a highly conserved amino acid, with proline (P) being substituted by threonine (T) (p.P544T). Functional analysis shows that this amino-acid substitution compromises both tri- and didemethylase activity of the JARID1C protein. We conclude that the two novel changes impair JARID1C protein function and are disease-causing mutations in these families.]]> Sat 24 Mar 2018 08:12:38 AEDT ]]> CASK mutations are frequent in males and cause X-linked nystagmus and variable XLMR phenotypes https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:10278 T) in two small families with nystagmus and MR. Detailed clinical examinations of all six families, including an ophthalmological review in four families, were undertaken to further characterise the phenotype. We report on the clinical features of 24 individuals, mostly male, from six families with CASK mutations. The phenotype was variable, ranging from non-syndromic mild MR to severe MR associated with microcephaly and dysmorphic facial features. Carrier females were variably affected. Congenital nystagmus was found in members of four of the families. Our findings reinforce the CASK gene as a relatively frequent cause of XLMR in females and males. We further define the phenotypic spectrum and demonstrate that affected males with missense mutations or in-frame deletions in CASK are frequently associated with congenital nystagmus and XLMR, a striking feature not previously reported.]]> Sat 24 Mar 2018 08:09:09 AEDT ]]> Submicroscopic duplications of the hydroxysteroid dehydrogenase HSD17B10 and the E3 ubiquitin ligase HUWE1 are associated with mental retardation https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:5093 Sat 24 Mar 2018 07:48:50 AEDT ]]> A novel X-linked trichothiodystrophy associated with a nonsense mutation in RNF113A https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:24614 T, p.Q301*). The mutation segregated with the disease in the family and was not observed in over 100 000 control X chromosomes. The mutation markedly reduced RNF113A protein expression in extracts from lymphoblastoid cell lines derived from the affected individuals. Conclusions: The association of RNF113A mutation with non-photosensitive TTD identifies a new locus for these disorders on the X chromosome. The extended phenotype within this family includes panhypopituitarism, cutis marmorata and congenital short oesophagus.]]> Sat 24 Mar 2018 07:11:55 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 ]]> Cerebellar volume mediates the relationship between FMR1 mRNA levels and voluntary step initiation in males with the premutation https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:32065 FMR1) gene show postural control deficits that may reflect disruption to cerebellar motor regions. Less is known about the influence of reduced cerebellar volume and structural changes, and increase in CGG repeat and FMR1 mRNA levels on the attentional demands of step initiation in PM males. We investigated the effects of a concurrent cognitive task on choice stepping reaction time (CSRT) and explored the associations between CSRT performance, cerebellar volume, CGG size, and FMR1 mRNA levels in blood in PM males. We examined 19 PM males (ages 28–75) and 23 matched controls (CGG <44; ages 26–77), who performed a verbal fluency task during CSRT performance and single-task stepping without a secondary cognitive task. Our results provide preliminary evidence that smaller cerebellar volume (β = −2.73, p = 0.002) and increasing CGG repeat length (β = 1.69, p = 0.003) were associated with greater dual-task step initiation times in PM males, but not in controls. There was evidence of a mediating effect of cerebellar volume on the relationship between FMR1 mRNA levels and single-task CSRT performance in PM males (estimate coefficient = 8.69, standard error = 4.42, p = 0.049). These findings suggest increasing CGG repeat and FMR1 mRNA levels have neurotoxic effects on cerebellar regions underlying anticipatory postural responses during stepping. Cerebellar postural changes may be predictive of the increased risk of falls in older PM males.]]> Fri 27 Apr 2018 09:46:49 AEST ]]>