Alexander M. Rossor
A5001878666- Hereditary Neurological Disorders
- Genetic Neurodegenerative Diseases
- Neurological diseases and metabolism
- Peripheral Neuropathies and Disorders
- Neurogenetic and Muscular Disorders Research
- Botulinum Toxin and Related Neurological Disorders
- Mitochondrial Function and Pathology
- RNA regulation and disease
- Cellular transport and secretion
- Endoplasmic Reticulum Stress and Disease
- Heat shock proteins research
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Cardiomyopathy and Myosin Studies
- RNA Research and Splicing
- Metabolism and Genetic Disorders
- Platelet Disorders and Treatments
- Microtubule and mitosis dynamics
- Muscle Physiology and Disorders
- Autoimmune Neurological Disorders and Treatments
- RNA modifications and cancer
- Peripheral Nerve Disorders
- Skin and Cellular Biology Research
- Dermatological and Skeletal Disorders
- Myasthenia Gravis and Thymoma
- Alcoholism and Thiamine Deficiency
National Hospital for Neurology and Neurosurgery
2016-2025
University College London
2016-2025
Guy's and St Thomas' NHS Foundation Trust
2023-2025
St. Thomas Hospital
2015-2024
St Thomas' Hospital
2024
John Wiley & Sons (United States)
2024
Hudson Institute
2024
University of Iowa
2019-2021
Sanofi (United States)
2021
University of Wisconsin–Madison
2021
Volumetric magnetic resonance imaging analyses of 30 subjects were undertaken to quantify the global and temporal lobe atrophy in semantic dementia Alzheimer's disease. Three groups 10 studied: patients, disease control subjects. The structures measured amygdala, hippocampus, entorhinal cortex, parahippocampal gyrus, fusiform superior, middle, inferior gyri. Semantic did not differ significantly on measures. In dementia, there was asymmetrical atrophy, with greater left-sided damage. There...
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...
<h3>Objective</h3> To perform a cross-sectional study to determine whether plasma neurofilament light chain (NfL) concentration is elevated in patients with Charcot-Marie-Tooth disease (CMT) and if it correlates severity. <h3>Methods</h3> Blood samples were collected from 75 CMT 67 age-matched healthy controls over 1-year period. Disease severity was measured using the Rasch modified Examination neuropathy scores. Plasma NfL an in-house-developed Simoa assay. <h3>Results</h3> significantly...
Ataxia, causing imbalance, dizziness and falls, is a leading cause of neurological disability. We have recently identified biallelic intronic AAGGG repeat expansion in replication factor complex subunit 1 (RFC1) as the cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) major late onset ataxia. Here we describe full spectrum disease phenotype our first 100 genetically confirmed carriers expansions RFC1 identify sensory neuropathy common feature all cases to date. All...
To expand the clinical phenotype of autosomal dominant congenital spinal muscular atrophy with lower extremity predominance (SMA-LED) due to mutations in dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) gene.Patients a suggestive motor, non-length-dependent neuronopathy predominantly affecting limbs were identified at participating neuromuscular centers and referred for targeted sequencing DYNC1H1.We report cohort 30 cases SMA-LED from 16 families, carrying tail motor domains DYNC1H1,...
<h3>Objective</h3> To measure the frequency, persistence, isoform specificity, and clinical correlates of neurofascin antibodies in patients with peripheral neuropathies. <h3>Methods</h3> We studied cohorts Guillain-Barre syndrome (GBS) or chronic inflammatory demyelinating polyneuropathy (CIDP) (n = 59), genetic neuropathy 111), idiopathic 43) for immunoglobulin (Ig) G IgM responses to 3 (NF) isoforms (NF140, NF155, NF186) using cell-based assays. <h3>Results</h3> Neurofascin were more...
To investigate the effectiveness of targeted next-generation sequencing (NGS) panels in achieving a molecular diagnosis Charcot-Marie-Tooth disease (CMT) and related disorders clinical setting.We prospectively enrolled 220 patients from 2 tertiary referral centers, one London, United Kingdom (n = 120), Iowa 100), whom CMT NGS panel had been requested as diagnostic test. PMP22 duplication/deletion was previously excluded demyelinating cases. We reviewed genetic data upon completion...
After extensive evaluation, one-third of patients affected by polyneuropathy remain undiagnosed and are labelled as having chronic idiopathic axonal polyneuropathy, which refers to a sensory or sensory-motor, axonal, slowly progressive neuropathy unknown origin. Since neuropathy/neuronopathy is identified in all with genetically confirmed RFC1 cerebellar ataxia, neuropathy, vestibular areflexia syndrome, we speculated that expansions could underlie fraction neuropathies also diagnosed...
Abstract Charcot-Marie-Tooth disease (CMT) is one of the most common and genetically heterogeneous inherited neurological diseases, with more than 130 disease-causing genes. Whole genome sequencing (WGS) has improved diagnosis across genetic but diagnostic impact in CMT yet to be fully reported. We present results from a single specialist neuropathy centre, including WGS testing. Patients were assessed at our centre 2009 2023. Genetic testing was performed using gene testing, next-generation...
Abstract Oculopharyngodistal myopathy (OPDM) is an inherited manifesting with ptosis, dysphagia and distal weakness. Pathologically it characterised by rimmed vacuoles intranuclear inclusions on muscle biopsy. In recent years CGG • CCG repeat expansion in four different genes were identified OPDM individuals Asian populations. None of these have been found affected non-Asian ancestry. this study we describe the identification expansions ABCD3 , ranging from 118 to 694 repeats, 35 across...
Abstract RFC1 disease, caused by biallelic repeat expansion in RFC1, is clinically heterogeneous terms of age onset, disease progression and phenotype. We investigated the role size influencing clinical variables disease. also assessed presence meiotic somatic instability repeat. In this study, we identified 553 patients carrying expansions measured 392 cases. Pearson’s coefficient was calculated to assess correlation between at onset. A Cox model with robust cluster standard errors adopted...
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,...
Leukodystrophies and genetic leukoencephalopathies are a rare group of disorders leading to progressive degeneration cerebral white matter. They associated with spectrum clinical phenotypes dominated by dementia, psychiatric changes, movement upper motor neuron signs. Mutations in at least 60 genes can lead leukoencephalopathy often overlapping radiological presentations. For these reasons, patients endure long diagnostic odyssey before receiving definitive diagnosis or may receive no all....
MFN2 encodes mitofusin 2, a membrane-bound mediator of mitochondrial membrane fusion and inter-organelle communication. mutations cause axonal neuropathy, with associated lipodystrophy only occasionally noted, however homozygosity for the p.Arg707Trp mutation was recently upper body adipose overgrowth. We describe similar massive overgrowth suppressed leptin expression in four further patients biallelic at least one allele. Overgrown tissue composed normal-sized, UCP1-negative unilocular...
Abstract Mitofusin-2 (MFN2) is one of two ubiquitously expressed homologous proteins in eukaryote cells, playing a critical role mitochondrial fusion. Mutations MFN2 (most commonly autosomal dominant) cause Charcot-Marie-Tooth disease type 2A (CMT2A), the commonest axonal form CMT, with significant allelic heterogeneity. Previous, moderately-sized, cross sectional genotype-phenotype studies CMT2A have described phenotypic spectrum disease, but longitudinal natural history are lacking. In...