https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:45162 FGF12 are associated with intractable seizures, developmental regression, intellectual disability, ataxia, hypotonia, and feeding difficulties. FGF12 duplications are rarely reported, but it was suggested that those might have a similar gain-of-function effect and lead to a more or less comparable phenotype. A favorable response to the sodium blocker phenytoin was reported in several cases, both in patients with an intragenic mutation and in patients with a duplication of FGF12. We report three individuals from two families with FGF12 duplications. The duplications are flanked and probably mediated by two long interspersed nuclear elements (LINEs). The duplication cases show phenotypic overlap with the cases with intragenic mutations. Though the onset of epilepsy might be later, after the onset of seizures both groups show developmental stagnation and regression in several cases. This illustrates and further confirms that chromosomal FGF12 duplications and intragenic gain-of-function mutations yield overlapping phenotypes.]]> Wed 26 Oct 2022 19:18:45 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:35585 Wed 24 May 2023 12:08:33 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:56005 Wed 17 Jul 2024 13:38:11 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:55998 Wed 17 Jul 2024 13:31:13 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:22010 Wed 14 Aug 2024 15:58:54 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:35839 Wed 11 Dec 2019 09:39:28 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:9934 Wed 11 Apr 2018 14:37:09 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:31227 Wed 11 Apr 2018 14:09:18 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:13433 Wed 11 Apr 2018 10:01:56 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:42920 Wed 07 Sep 2022 13:13:35 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:34063 Wed 06 Apr 2022 14:02:02 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:56303 Wed 04 Sep 2024 11:50:52 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:49050 Wed 03 May 2023 15:40:01 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:42245 Tue 21 Mar 2023 19:04:35 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:40885 Tue 19 Jul 2022 14:59:14 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:55161 Tue 16 Apr 2024 15:43:27 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:53025 Tue 14 Nov 2023 14:30:04 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:22495 Thu 22 Sep 2016 11:23:42 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:33338 Thu 18 Oct 2018 15:29:00 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:41484 DDX3X have recently been identified to be a relatively common cause of intellectual disability in females. In this study, we describe six female probands, from five unrelated families, with five novel heterozygous variants in DDX3X, and the identification of potential germline mosaicism. Consistent features between this cohort and previously described cases include developmental delay or intellectual disability, growth disturbance and movement disorder. Common facial dysmorphism within the cohort include short palpebral fissures, micrognathia, bulbous nasal tip, protruding ears, high arched palate, thin upper vermillion and smooth philtrum. Novel clinical features identified from this cohort include facial dysmorphisms, perinatal complications, valgus feet deformity, lipoatrophy, dystonic episodes, and cutaneous mastocytosis. This case series attempts to expand the phenotype of the DDX3X syndrome; however, it remains heterogeneous. Description of further cases is required to more accurately identify the significance of novel phenotypes within this cohort.]]> Thu 04 Aug 2022 14:36:40 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:4519 Sat 24 Mar 2018 10:12:58 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:8673 Sat 24 Mar 2018 08:36:10 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:16041 Sat 24 Mar 2018 08:22:56 AEDT ]]> https://novaprd-lb.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://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:16892 Sat 24 Mar 2018 08:00:47 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:29695 Sat 24 Mar 2018 07:38:48 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:28674 Sat 24 Mar 2018 07:37:10 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:27451 Sat 24 Mar 2018 07:32:46 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:24337 Sat 24 Mar 2018 07:16:38 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:22371 Sat 24 Mar 2018 07:09:29 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:45536 Mon 31 Oct 2022 15:33:57 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:14294 Mon 19 Aug 2024 11:36:39 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:52313 Mon 09 Oct 2023 10:23:33 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:37229 Mon 07 Sep 2020 16:03:08 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:35449 Fri 16 Aug 2019 15:13:27 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:39078 de novo CNOT1 variants, including missense, splice site, and nonsense variants, who present with a clinical spectrum of intellectual disability, motor delay, speech delay, seizures, hypotonia, and behavioral problems. To link CNOT1 dysfunction to the neurodevelopmental phenotype observed, we generated variant-specific Drosophila models, which showed learning and memory defects upon CNOT1 knockdown. Introduction of human wild-type CNOT1 was able to rescue this phenotype, whereas mutants could not or only partially, supporting our hypothesis that CNOT1 impairment results in neurodevelopmental delay. Furthermore, the genetic interaction with autism-spectrum genes, such as ASH1L, DYRK1A, MED13, and SHANK3, was impaired in our Drosophila models. Molecular characterization of CNOT1 variants revealed normal CNOT1 expression levels, with both mutant and wild-type alleles expressed at similar levels. Analysis of protein-protein interactions with other members indicated that the CCR4-NOT complex remained intact. An integrated omics approach of patient-derived genomics and transcriptomics data suggested only minimal effects on endonucleolytic nonsense-mediated mRNA decay components, suggesting that de novo CNOT1 variants are likely haploinsufficient hypomorph or neomorph, rather than dominant negative. In summary, we provide strong evidence that de novo CNOT1 variants cause neurodevelopmental delay with a wide range of additional co-morbidities. Whereas the underlying pathophysiological mechanism warrants further analysis, our data demonstrate an essential and central role of the CCR4-NOT complex in human brain development.]]> Fri 06 May 2022 12:37:33 AEST ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:45695 Fri 04 Nov 2022 10:01:23 AEDT ]]> https://novaprd-lb.newcastle.edu.au/vital/access/ /manager/Repository/uon:49824 Fri 02 Jun 2023 16:31:54 AEST ]]>