https://nova.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50624 Wed 28 Feb 2024 16:07:02 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42920 Wed 07 Sep 2022 13:13:35 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29133 Wed 07 Jul 2021 12:14:12 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49050 Wed 03 May 2023 15:40:01 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:32529 de novo missense variant within the C-terminal Sin3-like domain of ZSWIM6 was previously reported to cause acromelic frontonasal dysostosis (AFND), an autosomal-dominant severe frontonasal and limb malformation syndrome, associated with neurocognitive and motor delay, via a proposed gain-of-function effect. We present detailed phenotypic information on seven unrelated individuals with a recurrent de novo nonsense variant (c.2737C > T [p.Arg913Ter]) in the penultimate exon of ZSWIM6 who have severe-profound intellectual disability and additional central and peripheral nervous system symptoms but an absence of frontonasal or limb malformations. We show that the c.2737C > T variant does not trigger nonsense-mediated decay of the ZSWIM6 mRNA in affected individual-derived cells. This finding supports the existence of a truncated ZSWIM6 protein lacking the Sin3-like domain, which could have a dominant-negative effect. This study builds support for a key role for ZSWIM6 in neuronal development and function, in addition to its putative roles in limb and craniofacial development, and provides a striking example of different variants in the same gene leading to distinct phenotypes.]]> Thu 16 Aug 2018 10:03:57 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:44086 Thu 06 Oct 2022 15:34:32 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:8169 Sat 24 Mar 2018 08:36:05 AEDT ]]> https://nova.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 ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:10275 Sat 24 Mar 2018 08:13:04 AEDT ]]> https://nova.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 ]]> https://nova.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 ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:5122 Sat 24 Mar 2018 07:48:57 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:5320 Sat 24 Mar 2018 07:45:58 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28674 Sat 24 Mar 2018 07:37:10 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:3341 Sat 24 Mar 2018 07:22:35 AEDT ]]>