Stéphanie Efthymiou
A5027430673- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Mitochondrial Function and Pathology
- Hereditary Neurological Disorders
- Genetic Neurodegenerative Diseases
- RNA regulation and disease
- RNA modifications and cancer
- Cellular transport and secretion
- Neurogenetic and Muscular Disorders Research
- Neurological diseases and metabolism
- RNA Research and Splicing
- Metabolism and Genetic Disorders
- Genomic variations and chromosomal abnormalities
- RNA and protein synthesis mechanisms
- Lysosomal Storage Disorders Research
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- Epilepsy research and treatment
- Ion channel regulation and function
- Connective tissue disorders research
- Autism Spectrum Disorder Research
- Glycosylation and Glycoproteins Research
- CRISPR and Genetic Engineering
- Neurological disorders and treatments
University College London
2016-2025
National Hospital for Neurology and Neurosurgery
2016-2025
The Francis Crick Institute
2024
Cyprus Institute of Neurology and Genetics
2024
Istituto Giannina Gaslini
2024
Istituti di Ricovero e Cura a Carattere Scientifico
2024
University of Wisconsin–Madison
2023
Erasmus MC
2023
B.C. Women's Hospital & Health Centre
2022
John Wiley & Sons (United States)
2021
Abstract AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca 2+ -impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients intellectual disability (ID) neurodevelopmental...
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...
Primary familial brain calcification (PFBC) is characterized by calcium deposition in the brain, causing progressive movement disorders, psychiatric symptoms, and cognitive decline. PFBC a heterogeneous disorder currently linked to variants six different genes, but most patients remain genetically undiagnosed. Here, we identify biallelic NAA60 ten individuals from seven families with autosomal recessive PFBC. The lead loss-of-function lack of protein N-terminal (Nt)-acetylation activity. We...
Genetic diagnosis of rare diseases requires accurate identification and interpretation genomic variants. Clinical molecular scientists from 37 expert centers across Europe created the Solve-Rare Diseases Consortium (Solve-RD) resource, encompassing clinical, pedigree rare-disease data (94.5% exomes, 5.5% genomes), performed systematic reanalysis for 6,447 individuals (3,592 male, 2,855 female) with previously undiagnosed 6,004 families. We established a collaborative, two-level review...
<ns4:p>Intellectual disability (ID) is a neurodevelopmental condition affecting 1–3% of the world’s population. Genetic factors play key role causing congenital limitations in intellectual functioning and adaptive behavior. The heterogeneity ID makes it more challenging for genetic clinical diagnosis, but advent large-scale genome sequencing projects trio approach has proven very effective. However, many variants are still difficult to interpret. A combined next-generation functional,...
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...
PRUNE is a member of the DHH (Asp-His-His) phosphoesterase protein superfamily molecules important for cell motility, and implicated in cancer progression. Here we investigated multiple families from Oman, India, Iran Italy with individuals affected by new autosomal recessive neurodevelopmental degenerative disorder which cardinal features include primary microcephaly profound global developmental delay. Our genetic studies identified biallelic mutations PRUNE1 as responsible. functional...
Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by combination of neurological, psychiatric, and cognitive decline associated with calcium deposition on imaging. To date, mutations in five genes have been linked to PFBC. However, more than 50% individuals affected PFBC no molecular diagnosis. We report four unrelated families presenting initial learning difficulties seizures later psychiatric symptoms, cerebellar ataxia, extrapyramidal signs,...
Objective To identify disease‐causing variants in autosomal recessive axonal polyneuropathy with optic atrophy and provide targeted replacement therapy. Methods We performed genome‐wide sequencing, homozygosity mapping, segregation analysis for novel gene discovery. used circular dichroism to show secondary structure changes isothermal titration calorimetry investigate the impact of on adenosine triphosphate (ATP) binding. Pathogenicity was further supported by enzymatic assays mass...
ABSTRACT Background: We investigated a family that presented with an infantile‐onset chorea‐predominant movement disorder, negative for NKX2‐1, ADCY5 , and PDE10A mutations. Methods: Phenotypic characterization trio whole‐exome sequencing was carried out in the family. Results: identified homozygous mutation affecting GAF‐B domain of 3’,5’‐cyclic nucleotide phosphodiesterase PDE2A gene (c.1439A>G; p.Asp480Gly) as candidate novel genetic cause chorea proband. hydrolyzes cyclic...
See Karakaya and Wirth (doi:10.1093/brain/awz273) for a scientific commentary on this article. Neurofascin (NFASC) isoforms are immunoglobulin cell adhesion molecules involved in node of Ranvier assembly. Efthymiou et al. identify biallelic NFASC variants ten unrelated patients with neurodevelopmental disorder characterized by variable degrees central peripheral involvement. Abnormal expression Nfasc155 is accompanied severe loss myelinated fibres.
Abstract Neuronal intranuclear inclusion disease (NIID) is a clinically heterogeneous neurodegenerative condition characterized by pathological eosinophilic inclusions. A CGG repeat expansion in NOTCH2NLC was recently identified to be associated with NIID patients of Japanese descent. We screened pathologically confirmed European NIID, cases inclusions and applied silico‐based screening using whole‐genome sequencing data from 20 536 participants the 100 000 Genomes Project. single case...
This study was undertaken to identify susceptibility loci for cluster headache and obtain insights into relevant disease pathways.We carried out a genome-wide association study, where 852 UK 591 Swedish cases were compared with 5,614 1,134 controls, respectively. Following quality control imputation, single variant testing conducted using logistic mixed model each cohort. The 2 cohorts subsequently combined in merged analysis. Downstream analyses, such as gene-set enrichment, functional...
Inherited glycosylphosphatidylinositol deficiency disorders (IGDs) are a group of rare multisystem arising from pathogenic variants in anchor pathway (GPI-AP) genes. Despite associating 24 at least 31 GPI-AP genes with human neurogenetic disease, prior reports limited to single without consideration the as whole and natural history data. In this multinational retrospective observational study, we systematically analyse molecular spectrum, phenotypic characteristics 83 individuals 75 unique...
We report 2 families with undiagnosed recessive presynaptic congenital myasthenic syndrome (CMS). Whole exome or genome sequencing identified segregating homozygous variants in VAMP1: c.51_64delAGGTGGGGGTCCCC a Kuwaiti family and c.146G>C an Israeli family. VAMP1 is crucial for vesicle fusion at neuromuscular junction (NMJ). Electrodiagnostic examination showed severely low compound muscle action potentials impairment. assessed the effect of nonsense mutation on mRNA levels evaluated NMJ...
Developmental and/or epileptic encephalopathies (DEEs) are a group of devastating genetic disorders, resulting in early-onset, therapy-resistant seizures and developmental delay. Here we report on 22 individuals from 15 families presenting with severe form intractable epilepsy, delay, progressive microcephaly, visual disturbance similar minor dysmorphisms. Whole exome sequencing identified recurrent, homozygous variant (chr2:64083454A > G) the essential UDP-glucose pyrophosphorylase (UGP2)...
We report on a homozygous frameshift deletion in DDX59 (c.185del: p.Phe62fs*13) family presenting with orofaciodigital syndrome phenotype associated broad neurological involvement characterized by microcephaly, intellectual disability, epilepsy, and white matter signal abnormalities cortical subcortical ischemic events. encodes DEAD-box RNA helicase its role brain function diseases is unclear. showed reduction of mutant cDNA perturbation SHH signaling from patient-derived cell lines;...
Aminoacyl-tRNA synthetases (ARSs) are ubiquitous, ancient enzymes that charge amino acids to cognate tRNA molecules, the essential first step of protein translation. Here, we describe 32 individuals from 21 families, presenting with microcephaly, neurodevelopmental delay, seizures, peripheral neuropathy, and ataxia, de novo heterozygous bi-allelic mutations in asparaginyl-tRNA synthetase (NARS1). We demonstrate a reduction NARS1 mRNA expression as well enzyme levels activity both individual...
NTNG2 encodes netrin-G2, a membrane-anchored protein implicated in the molecular organization of neuronal circuitry and synaptic diversification vertebrates. In this study, through combination exome sequencing autozygosity mapping, we have identified 16 individuals (from seven unrelated families) with ultra-rare homozygous missense variants NTNG2; these present shared features neurodevelopmental disorder consisting global developmental delay, severe to profound intellectual disability,...
Human 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) is a putative iron-containing non-heme oxygenase of unknown specificity and biological significance. We report 25 families containing 34 individuals with neurological disease associated biallelic HPDL variants. Phenotypes ranged from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spasticity global developmental delays, sometimes complicated by episodes respiratory decompensation. Variants included bona fide...