A5057278511- Epilepsy research and treatment
- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Pharmacological Effects and Toxicity Studies
- Mitochondrial Function and Pathology
- Genomic variations and chromosomal abnormalities
- Cardiac electrophysiology and arrhythmias
- Metabolism and Genetic Disorders
- Nicotinic Acetylcholine Receptors Study
- RNA and protein synthesis mechanisms
- Molecular Sensors and Ion Detection
- Genetic Associations and Epidemiology
- Ion Transport and Channel Regulation
- Hemoglobinopathies and Related Disorders
- Genetic factors in colorectal cancer
- Amino Acid Enzymes and Metabolism
- Microtubule and mitosis dynamics
- Neonatal Respiratory Health Research
- Bipolar Disorder and Treatment
- Genetic Neurodegenerative Diseases
- Receptor Mechanisms and Signaling
- Glycogen Storage Diseases and Myoclonus
- Cellular transport and secretion
Swansea University
2015-2025
The University of Sydney
2019-2025
Swansea Bay University Health Board
2021-2023
University of Malaya
2023
University of Copenhagen
2023
Filadelfia
2023
King's College London
2022-2023
King's College Hospital
2022
Morriston Hospital
2001-2021
Cleveland Clinic Lerner College of Medicine
2020
Glycine receptors (GlyRs) and specific subtypes of GABA A are clustered at synapses by the multidomain protein gephyrin, which in turn is translocated to cell membrane GDP-GTP exchange factor collybistin. We report characterization several new variants collybistin, created alternative splicing exons encoding an N-terminal src homology 3 (SH3) domain three alternate C termini (CB1, CB2, CB3). The presence SH3 negatively regulates ability collybistin translocate gephyrin submembrane...
Hyperekplexia (MIM: 149400) is a neurological disorder characterized by an excessive startle response which can be caused mutations in the α1-subunit (GLRA1) of heteropentameric human inhibitory glycine receptor (hGlyR). These receptors facilitate fast-response, glycinergic neurotransmission brainstem and spinal cord leading to rapid modification reduction excitatory response. Mutations β-subunit GlyR (glrb) occur murine model hyperekplexia (spastic), but have not been detected...
We previously showed that mutations in LIS1 and DCX account for ∼85% of patients with the classic form lissencephaly (LIS). Some rare forms LIS are associated a disproportionately small cerebellum, referred to as cerebellar hypoplasia (LCH). Tubulin alpha1A (TUBA1A), encoding critical structural subunit microtubules, has recently been implicated LIS. Here, we screen largest cohort unexplained examined date determine: (i) frequency TUBA1A lissencephaly, (ii) spectrum phenotypes (iii)...
In response to reported schizophrenia linkage findings on chromosomes 3, 6 and 8, fourteen research groups genotyped 14 microsatellite markers in an unbiased, collaborative (New) sample of 403–567 informative pedigrees per marker, the Original which produced each finding (the Johns Hopkins University 46–52 for 3 Medical College Virginia 156–191 chromosome 6). Primary planned analyses (New sample) were two-point heterogeneity lod score (lod2) tests (dominant recessive affected-only models),...
Huntington's disease (HD) is an inherited autosomal dominant neurodegenerative disorder caused by expansion of a CAG trinucleotide repeat in the huntingtin (HTT) gene [Huntington's Disease Collaborative Research Group (1993) A novel containing that expanded and unstable on chromosomes. The Group. Cell, 72, 971–983]. Despite identification 1993, underlying life-long process effective treatments to prevent or delay it remain elusive. In effort fast-track treatment strategies for HD into...
Abstract Myelin loss is frequently observed in human Alzheimer's disease (AD) and may constitute to AD‐related cognitive decline. A potential source repair myelin defects are the oligodendrocyte progenitor cells (OPCs) present an adult brain. However, until now, little known about reaction of these toward amyloid plaque deposition neither AD patients nor appropriate mouse models. Therefore, we analyzed lineage a model with chronic (APPPS1 mice) samples from patients. In APPPS1 mice integrity...
Polymicrogyria and lissencephaly are causally heterogeneous disorders of cortical brain development, with distinct neuropathological neuroimaging patterns. They can be associated additional structural cerebral anomalies, recurrent phenotypic patterns have led to identification recognizable syndromes. The lissencephalies usually single-gene affecting neuronal migration during development. has been genetic environmental causes is considered a malformation secondary abnormal post-migrational...
Cortical gray matter (GM) pathology, involving demyelination and neurodegeneration, associated with meningeal inflammation, could be important in determining disability progression multiple sclerosis (MS). However, we need to know more about how cortical demyelination, inflammation contribute pathology at early stages of MS better predict long-term outcome.Tissue blocks from short disease duration (n = 12, median 2 years), progressive 21, 25 non-diseased controls 11), other neurological...
The symptoms of multiple sclerosis (MS) are caused by damage to myelin and nerve cells in the brain spinal cord. Inflammation is tightly linked with neurodegeneration, it accumulation neurodegeneration that underlies increasing neurological disability progressive MS. Determining pathological mechanisms at play MS grey matter therefore a key our understanding disease progression. We analysed complement expression activation immunocytochemistry situ hybridisation frozen or formalin-fixed...
Polymicrogyria is a malformation of cortical development. The aetiology polymicrogyria remains poorly understood. Using whole-exome sequencing we found de novo heterozygous missense GRIN1 mutations in 2 57 parent-offspring trios with polymicrogyria. We nine further additional patients. Shared features the patients were extensive bilateral associated severe developmental delay, postnatal microcephaly, visual impairment and intractable epilepsy. encodes GluN1, essential subunit...
<h3>Objective</h3> To characterize trends in incidence, prevalence, and health care outcomes the idiopathic intracranial hypertension (IIH) population Wales using routinely collected data. <h3>Methods</h3> We used validated primary secondary IIH diagnosis codes within Secure Anonymised Information Linkage databank to ascertain cases controls a retrospective cohort study between 2003 2017. recorded body mass index (BMI), deprivation quintile, CSF diversion surgery, unscheduled hospital...
We undertook a systematic search for linkage in 196 affected sibling pairs (ASPs) with DSMIV schizophrenia. In stage 1 we typed 97ASPs 229 microsatellite markers at an average inter-marker distance of 17.26 cM. Multipoint sib pair analysis identified seven regions maximum lod score (MLS) or above the level associated nominal pointwise significance 5%, on chromosomes 2q, 4p, 10q, 15q, 18p, 20q and Xcen. 2 genotyped further 54 ASPs together parents unaffected siblings. This allowed to be...
Journal Article Evidence for recessive as well dominant forms of startle disease (hyperekplexia) caused by mutations in the α1 subunit inhibitory glycine receptor Get access Mark I. Rees, Rees 1Departments Psychological Medicine, University Wales College MedicineHealth Park, Cardiff CF4, 4XN, UK2Medical Genetics, CF4 UK Search other works this author on: Oxford Academic PubMed Google Scholar Martin Andrew, Andrew Sudad Jawad, Jawad Michael J. Owen Human Molecular Volume 3, Issue 12, December...
Hyperekplexia is a rare, but potentially fatal, neuromotor disorder characterized by exaggerated startle reflexes and hypertonia in response to sudden, unexpected auditory or tactile stimuli. This primarily caused inherited mutations the genes encoding glycine receptor (GlyR) alpha1 subunit (GLRA1) presynaptic transporter GlyT2 (SLC6A5). In this study, systematic DNA sequencing of GLRA1 88 new unrelated human hyperekplexia patients revealed 19 sequence variants 30 index cases, which 21 cases...
Summary The intra‐operative blood loss of 50 consecutive gynae‐oncology patients undergoing surgery for endometrial, cervical or ovarian cancer was cell salvaged and filtered. In each case samples were taken from the effluent tumour vein, a central venous line, saver reservoir, salvage re‐transfusion bag after processing but before filtration filtration. Samples examined using immunohistochemical monoclonal antibody markers epithelial lines. Viable, nucleated malignant cells detected in 2/50...
Mutations in alpha- and beta-tubulins are increasingly recognized as a major cause of malformations cortical development (MCD), typically lissencephaly, pachygyria polymicrogyria; however, sequencing tubulin genes large cohorts MCD patients has detected mutations only 1–13%. We identified with highly characteristic cerebellar dysplasia but without polymicrogyria associated mutations. Remarkably, seven nine (78%), targeted revealed three different (TUBA1A, TUBB2B TUBB3), occurring de novo or...
Sudden unexpected death in epilepsy (SUDEP) represents the most severe degree of spectrum severity and is commonest cause epilepsy-related premature mortality.The precise pathophysiology genetic architecture SUDEP remain elusive.Aiming to elucidate basis SUDEP, we analysed rare, protein-changing variants from whole-exome sequences 18 people who died 87 living with 1479 non-epilepsy disease controls.Association analysis revealed a significantly increased genome-wide polygenic burden per...