A5064741797- Genetic Neurodegenerative Diseases
- Hereditary Neurological Disorders
- Mitochondrial Function and Pathology
- Neurological diseases and metabolism
- Botulinum Toxin and Related Neurological Disorders
- Peripheral Neuropathies and Disorders
- Acute Ischemic Stroke Management
- Cerebrovascular and Carotid Artery Diseases
- Cellular transport and secretion
- DNA Repair Mechanisms
- RNA regulation and disease
- RNA modifications and cancer
- Autoimmune Neurological Disorders and Treatments
- Metabolism and Genetic Disorders
- Genetics and Neurodevelopmental Disorders
- Cardiovascular Health and Disease Prevention
- Ubiquitin and proteasome pathways
- Endoplasmic Reticulum Stress and Disease
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Sports injuries and prevention
- Obesity, Physical Activity, Diet
- Urologic and reproductive health conditions
- Ophthalmology and Eye Disorders
- Nerve Injury and Rehabilitation
- Platelet Disorders and Treatments
Trinity College Dublin
2015-2024
Tallaght University Hospital
2015-2024
University College London
2010-2024
University College Hospital
2010-2024
Guy's and St Thomas' NHS Foundation Trust
2024
Harefield Hospital
2024
Rotunda Hospital
2023
University Hospital Kerry
2023
Temple Street Children's University Hospital
2015-2021
Children's Health Ireland at Crumlin
2021
Charcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous group of diseases with approximately 45 different causative genes described. The aims this study were to determine the frequency in large cohort patients CMT devise guidelines for genetic testing practice.The known cause sequenced 1607 (425 attending an inherited neuropathy clinic 1182 whose DNA was sent authors testing) proportion subtypes UK population.A molecular diagnosis achieved 62.6% clinic; 80.4% CMT1...
The Charcot‐Marie‐Tooth neuropathy score (CMTNS) is a reliable and valid composite comprising symptoms, signs, neurophysiological tests, which has been used in natural history studies of CMT1A CMT1X as an outcome measure treatment trials CMT1A. Following international workshop on measures disease (CMT), the CMTNS was modified to attempt reduce floor ceiling effects standardize patient assessment, aiming improve its sensitivity for detecting change over time effect intervention. After...
Membranous glomerulonephritis (MGN) is a common cause of nephrotic syndrome in adults, mediated by glomerular antibody deposition to an increasing number newly recognised antigens. Previous case reports have suggested association between patients with anti-contactin-1 (CNTN1)-mediated neuropathies and MGN. In observational study we investigated the pathobiology extent this potential MGN examining antibodies against CNTN1 clinical features cohort 468 suspected immune-mediated neuropathies,...
<h3>Objective:</h3> Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disorder, affecting 1 in 2,500 individuals. Mitochondrial DNA (mtDNA) mutations are not generally considered within differential diagnosis of patients with uncomplicated neuropathy, despite essential requirement ATP for axonal function. We identified mtDNA mutation m.9185T>C <i>MT-ATP6</i>, encoding ATP6 subunit mitochondrial synthase (OXPHOS complex V), at homoplasmic levels a family whom...
Spinal muscular atrophy is a disorder of lower motor neurons, most commonly caused by recessive mutations in SMN1 on chromosome 5q. Cases without are subclassified according to phenotype. atrophy, extremity-predominant, characterized limb muscle weakness and wasting, associated with reduced numbers lumbar neurons DYNC1H1, which encodes microtubule protein the dynein-dynactin complex one its cargo adaptors, BICD2. We have now identified 32 patients BICD2 from nine different families,...
Mutations in Bcl‐2 associated athanogene‐3 ( BAG3 ) are a rare cause of myofibrillar myopathy, characterised by rapidly progressive proximal and axial cardiomyopathy respiratory compromise. Neuropathy has been documented neurophysiologically previously reported cases ‐associated myopathy some giant axons were observed on nerve biopsies; however, neuropathy was not thought to be dominant feature the disease. In context inherited neuropathy, typically with autosomal recessive axonal caused...
Charcot-Marie-Tooth Neuropathy Score second version (CMTNSv2) is a validated clinical outcome measure developed for use in trials to monitor disease impairment and progression affected CMT patients. Currently, all items of CMTNSv2 have identical contribution the total score. We used Rasch analysis further explore psychometric properties CMTNSv2, particular, category response functioning, their weight on overall progression. Weighted responses represent more accurate estimate actual values...
The association between cancer, major surgery and venous thromboembolism (VTE) is well established. Multimodal therapy increasingly being used as standard treatment for localised gastrointestinal cancer. aim of this study was to examine the markers pro-coagulation response VTE risk in an exemplar multimodal model pre-operative combination chemotherapy radiation therapy, followed by complex cancer surgery. Consecutive patients (n=36) with oesophageal were studied at baseline after first...
Charcot‐Marie‐Tooth disease type 1X (CMT1X) is the second most common inherited peripheral neuropathy. Women with CMT1X typically have a less severe phenotype than men, perhaps because of X‐inactivation patterns. Our objective was to determine women and whether patterns in white blood cells (WBCs) differ between females controls. Thirty‐one were evaluated using CMT neuropathy score (CMTNS) symptom cross‐sectional longitudinal analyses. Lower scores correspond disability. WBCs analyzed for...
<h3>Objective:</h3> To describe the clinical and neurophysiologic phenotype of a family with hereditary sensory autonomic neuropathy type 1 (HSANI) due to novel mutation in <i>SPTLC2</i> characterize biochemical properties this mutation. <h3>Methods:</h3> We screened 107 patients HSAN who were negative for other genetic causes mutations <i>SPTLC2</i>. The new characterized cell-free cell-based activity assays. <h3>Results:</h3> A (A182P) was found 2 subjects single family. an...
<b>Background:</b> Cognitive impairment and dementia has been reported in autosomal dominant hereditary spastic paraparesis (HSP) linked to the SPG4 locus. There only one postmortem examination described; not all accept that progressive cognitive decline is a feature of this disorder. <b>Objective:</b> A family with SPG4-HSP known have deletion exon 17 spastin gene (SPG4delEx17) was cognitively assessed over 7-year period. The index member died performed. <b>Methods:</b> Thirteen members...
Charcot–Marie–Tooth disease (CMT) is the most common inherited neuropathy with heterogeneous clinical presentation and genetic background. The axonal form (CMT2) characterised by decreased action potentials indicating primary damage. underlying pathology involves degeneration which supposed to be related protein dysfunction caused various gene mutations. overlapping manifestation of CMT2 distal hereditary motor (dHMN) intermediate CMT causes further diagnostic difficulties. Aminoacyl-tRNA...
<h3>Importance</h3> Ataxia with oculomotor apraxia type 1 (AOA1) is an autosomal recessive cerebellar ataxia due to mutations in the aprataxin gene (<i>APTX</i>) that characterized by early-onset ataxia, apraxia, axonal motor neuropathy, and eventual decrease of albumin serum levels. <h3>Objectives</h3> To improve clinical, biomarker, molecular delineation AOA1 provide genotype-phenotype correlations. <h3>Design, Setting, Participants</h3> This retrospective analysis included biological...
Abstract Gait analysis of people with Charcot‐Marie‐Tooth (CMT) disease revealed proximal adaptive gait strategies to compensate for foot drop. We previously demonstrated that hip flexor muscle fatigue can limit walking endurance. This pilot study used a single‐blinded cross over design investigate the effect 16‐week home‐based programme resistance training on strength. Measures endurance, speed, exertion, fatigue, and general activity were also recorded. The exercise protocol was based...
1-Deoxysphingolipids (1-deoxySL) are atypical sphingolipids that formed by the enzyme serine palmitoyltransferase (SPT) due to a promiscuous use of L-alanine over its canonical substrate L-serine. Several mutations in SPT associated with hereditary sensory and autonomic neuropathy type I (HSAN1). The current hypothesis is these induce permanent shift affinity from L-serine toward which results pathologically increased 1-deoxySL formation HSAN1 patients. Also, wild-type forms under certain...
X-linked Charcot-Marie-Tooth disease (CMT1X) is the second most common cause of CMT, and usually caused by mutations in gap junction protein beta 1 (GJB1) gene which codes for connexin 32 (CX32). CX32 has three tissue-specific promoters, P1 specific liver pancreas, P1a liver, oocytes embryonic stem cells, P2 nerve-specific. Over 300 have been described GJB1, spread throughout coding region. We describe two families with inheritance a phenotype consistent CMT1X who did not GJB1 The non-coding...