Clare L. van Eyk
A5091459105- Genomics and Rare Diseases
- Cerebral Palsy and Movement Disorders
- Genetics and Neurodevelopmental Disorders
- RNA Research and Splicing
- Neurogenetic and Muscular Disorders Research
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Genomic variations and chromosomal abnormalities
- Cellular transport and secretion
- Autism Spectrum Disorder Research
- Family and Disability Support Research
- Genomics and Chromatin Dynamics
- Metabolism and Genetic Disorders
- RNA regulation and disease
- Microtubule and mitosis dynamics
- RNA modifications and cancer
- Retinal Development and Disorders
- Parkinson's Disease Mechanisms and Treatments
- Drug Transport and Resistance Mechanisms
- Cancer Genomics and Diagnostics
- Signaling Pathways in Disease
- Prenatal Screening and Diagnostics
- Viral Infectious Diseases and Gene Expression in Insects
- Fetal and Pediatric Neurological Disorders
- Insect Resistance and Genetics
The University of Adelaide
2013-2025
Inserm
2023
Université de Rouen Normandie
2023
Children's Mercy Hospital
2023
University Medical Center
2023
Centre Hospitalier Régional Universitaire de Brest
2023
Leipzig University
2023
Women's and Children's Hospital
2022
Australian Research Council
2012
Germline loss-of-function variants in CTNNB1 cause neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV; OMIM 615075) are the most frequent, recurrent monogenic of cerebral palsy (CP). We investigated range clinical phenotypes owing to disruptions determine association between NEDSDV CP.Genetic information from 404 individuals collectively 392 pathogenic were ascertained for study. From these, detailed 52 previously unpublished collected combined 68 published...
Abstract We implicated the X-chromosome THOC2 gene, which encodes largest subunit of highly-conserved TREX ( Tr anscription- Ex port) complex, in a clinically complex neurodevelopmental disorder with intellectual disability as core phenotype. To study molecular pathology this essential eukaryotic we generated mouse model based on hypomorphic Thoc2 exon 37–38 deletion variant patient ID, speech delay, hypotonia, and microcephaly. The male Δ/Y ) mice recapitulate phenotypes syndrome including...
Abstract Clustering Epilepsy (CE) is a neurological disorder caused by pathogenic variants of the Protocadherin 19 (PCDH19) gene. PCDH19 encodes protein involved in cell adhesion and Estrogen Receptor α mediated-gene regulation. To gain further insights into molecular role brain, we investigated interactome developing mouse hippocampus cortex. Combined with meta-analysis all reported interacting proteins, our results show that interacts proteins actin, microtubule, gene We report CAPZA1,...
The pathogenic agent responsible for the expanded repeat diseases, a group of neurodegenerative diseases that includes Huntington's disease is not yet fully understood. Expanded polyglutamine (polyQ) thought to be toxic in certain cases, however, all genes can encode polyQ sequence. Since repeat-containing RNA intermediary common these hairpin-forming single-stranded has been investigated as potential agent. More recently, it become apparent most loci have transcription occurring from both...
Cerebral palsy (CP) is the most frequent movement disorder of childhood affecting 1 in 500 live births developed countries. We previously identified likely pathogenic de novo or inherited single nucleotide variants (SNV) 14% (14/98) trios by exome sequencing and a further 5% (9/182) from evidence outlier gene expression using RNA sequencing. Here, we detected copy number (CNV) exomes 186 unrelated individuals with CP (including our original 98 trios) CoNIFER algorithm. CNV were validated...
Abstract Cerebral palsy (CP) is the most common cause of childhood physical disability, with incidence between 1/500 and 1/700 births in developed world. Despite increasing evidence for a major contribution genetics to CP aetiology, genetic testing currently not performed systematically. We assessed diagnostic rate genome sequencing (GS) clinically unselected cohort 150 singleton patients, confirmed at >4 years age. Clinical grade GS was on proband variants were filtered, classified...
ABSTRACT In 2016, Sifrim and colleagues described the first group of patients carrying heterozygous pathogenic variants in CDK13 sharing major clinical features mainly consisting congenital heart defects, intellectual disability peculiar facial (Congenital Heart Defects, Dysmorphic Facial Features, Intellectual Developmental Disorder; CHDFIDD, OMIM # 617360). This condition is generally referred to as ‐related disorder, since then other reports have provided further molecular information....
A growing body of evidence points to a considerable and heterogeneous genetic aetiology cerebral palsy (CP). To identify recurrently variant CP genes, we designed custom gene panel 112 candidate genes. We tested 366 clinically unselected singleton cases with CP, including 271 not previously examined using next-generation sequencing technologies. Overall, 5.2% the naïve (14/271) harboured clinical significance in known disease gene, further 4.8% individuals (13/271) having classified as...
Cerebral palsy (CP) is the most common motor disability of childhood. It characterised by permanent, non-progressive but not unchanging problems with movement, posture and function, a highly heterogeneous clinical spectrum frequent neurodevelopmental comorbidities. The aetiology CP poorly understood, despite recent reports genetic contribution in some cases. Here we demonstrate transcriptional dysregulation trophic signalling pathways patient-derived cell lines from an unselected cohort 182...
Recent evidence supports a role for RNA as common pathogenic agent in both the ‘polyglutamine’ and ‘untranslated’ dominant expanded repeat disorders. One feature of all sequences currently associated with disease is their predicted ability to form hairpin secondary structure at level. In order investigate mechanisms by which hairpin-forming RNAs could induce neurodegeneration, we have looked alterations gene transcript levels hallmarks cellular response toxic RNAs. Three disease-associated...
Homopolymeric amino acid repeat sequences in proteins are of particular interest due to the discovery that expanded copy numbers these repeats molecular basis for a growing list human genetic diseases. Repeat above typical normal range polyglutamine have been found be principal pathogenic agents number diseases, including Huntington's disease. There is emerging evidence expansions acids encoded by other reading frames CAG/CUG repeats, polyalanine and polyleucine, could contribute toxicity...
Aicardi Syndrome (AIC) is a rare neurodevelopmental disorder recognized by the classical triad of agenesis corpus callosum, chorioretinal lacunae and infantile epileptic spasms syndrome. The diagnostic criteria AIC were revised in 2005 to include additional phenotypes that are frequently observed this patient group. has been traditionally considered as X-linked male lethal because it almost exclusively affects females. Despite numerous genetic genomic investigations on AIC, unifying cause...
Abstract Neurons form the basic anatomical and functional structure of nervous system, defects in neuronal differentiation or formation neurites are associated with various psychiatric neurodevelopmental disorders. Dynamic changes cytoskeleton essential for this process, which is, inter alia, controlled by dedicator cytokinesis 4 ( DOCK4 ) through activation RAC1 . Here, we clinically describe 7 individuals (6 males one female) variants overlapping phenotype mild to severe global...
Understanding the impact of splicing and nonsense variants on RNA is crucial for resolution variant classification as well their suitability precision medicine interventions. This primarily enabled through studies involving transcriptomics followed by targeted assays using isolated from clinically accessible tissues (CATs) such blood or skin affected individuals. Insufficient disease gene expression in CATs does however pose a major barrier to based investigations, which we show relevant...