Svetlana Gorokhova
A5076760193- Muscle Physiology and Disorders
- Cardiomyopathy and Myosin Studies
- Genomics and Rare Diseases
- Neurogenetic and Muscular Disorders Research
- RNA Research and Splicing
- Genetic factors in colorectal cancer
- Hereditary Neurological Disorders
- Genetic Neurodegenerative Diseases
- Cellular transport and secretion
- Ion channel regulation and function
- Inflammatory Myopathies and Dermatomyositis
- Neurological diseases and metabolism
- Cancer Genomics and Diagnostics
- thermodynamics and calorimetric analyses
- Myasthenia Gravis and Thymoma
- Machine Learning in Materials Science
- Genetics and Neurodevelopmental Disorders
- Ubiquitin and proteasome pathways
- Nuclear Structure and Function
- Genomics and Phylogenetic Studies
- Nanopore and Nanochannel Transport Studies
- Biochemical and Molecular Research
- RNA modifications and cancer
- Chromatin Remodeling and Cancer
- Nerve injury and regeneration
Aix-Marseille Université
2015-2025
Inserm
2015-2025
Assistance Publique Hôpitaux de Marseille
2022-2025
Centre de Génétique Médicale de Marseille
2017-2024
Hôpital de la Timone
2019-2024
Génétique Médicale & Génomique Fonctionelle
2014-2024
National Institute of Neurological Disorders and Stroke
2021-2024
National Institutes of Health
2021-2024
Hôpital d'Enfants
2021
Institut de Biologie du Développement Marseille
2009-2014
We characterized a family consisting of four mammalian proteins unknown function (NKAIN1, 2, 3 and 4) single Drosophila ortholog dNKAIN. Aside from highly conserved transmembrane domains, NKAIN contain no functional domains. Striking amino acid conservation in the first two domains suggests that these are likely to within membrane bilayer. members neuronally expressed multiple regions mouse brain, although their expression is not ubiquitous. demonstrate NKAIN1 interacts with β1 subunit...
Many cancers cannot be detected early due to lack of effective disease biomarkers, leading poor prognosis. We applied an existing biophysical technology nanoDSF in a novel way answer this unmet biomedical need. developed breakthrough digital biomarker method for cancer detection based on AI-classification plasma denaturation profiles (PDPs) obtained by technology. PDPs from 300 samples patients with melanoma, brain, digestive or lung were automatically distinguished healthy accuracy 94%....
The major spliceosome contains five small nuclear RNAs (snRNAs; U1, U2, U4, U5 and U6) essential for splicing. Variants in RNU4-2, encoding cause a neurodevelopmental disorder called ReNU syndrome. We investigated de novo variants 50 snRNA-encoding genes French cohort of 23,649 individuals with rare disorders gathered additional cases through international collaborations. Altogether, we identified 145 previously unreported probands (likely) pathogenic RNU4-2 21 and/or recurrent RNU5B-1...
The most common autosomal recessive limb girdle muscular dystrophy is associated with the CAPN3 gene. exclusively inheritance of this disorder has been recently challenged by description recurrent variants, c.643_663del21 [p.(Ser215_Gly221del)] and c.598_612del15 [p.(Phe200_Leu204del)], dominant inheritance. Our objective was to confirm existence calpainopathies. Through our activity as one reference centres for genetic diagnosis calpainopathies in France resulting collaborations through...
Genome-wide sequencing is increasingly being performed during pregnancy to identify the genetic cause of congenital anomalies. The interpretation prenatally identified variants can be challenging and hampered by our often limited knowledge prenatal phenotypes. To better delineate phenotype Coffin-Siris syndrome (CSS), we collected clinical data from patients with a pathogenic variant in one CSS-associated genes.
Troponin I (TnI) regulates thin filament activation and muscle contraction. Two isoforms, TnI-fast ( TNNI2 ) TnI-slow TNNI1 ), are predominantly expressed in fast- slow-twitch myofibers, respectively. variants a rare cause of arthrogryposis, whereas have not been conclusively established to skeletal myopathy. We identified recessive loss-of-function as well dominant gain-of-function disease, each with distinct physiological consequences disease mechanisms. three families biallelic (F1:...
Massively parallel sequencing is rapidly becoming a widely used method in genetic diagnostics. However, there still no clear consensus as to which approach can most efficiently identify the pathogenic mutations carried by given patient, while avoiding false negative and positive results. We developed targeted exome (MyoPanel2) order optimize diagnosis of neuromuscular disorders. Using this approach, we were able analyse 306 genes known be mutated myopathies well related disorders, obtaining...
Stathmin is a prominent destabilizer of microtubules (MTs). Extensive in vitro studies have strongly suggested that stathmin could act by sequestering tubulin and/or binding to MT tips. In cells, the molecular mechanisms MTs and its implications for dynamics remain unexplored. By using immunofluorescence resonance energy transfer fluorescence recovery after photobleaching, we analyzed ability phosphorylated forms (on Ser16, −25, −38, −63) interact with A549 cells. Consistent studies,...
Improving the accuracy of variant interpretation during diagnostic sequencing is a major goal for genomic medicine. To explore an often-overlooked splicing effect missense variants, we developed functional assay ("minigene") majority exons CAPN3, gene responsible limb girdle muscular dystrophy. By systematically screening 21 variants distributed along gene, found that eight clinically relevant located at certain distance from exon-intron borders (deep exonic variants) disrupted normal CAPN3...
Abstract Background To describe the clinical, pathological, and molecular characteristics of late‐onset (LO) dysferlinopathy patients. Methods Retrospective series patients with LO dysferlinopathy, defined by an age at onset symptoms ≥30 years, from neuromuscular centers in France International Clinical Outcome Study for (COS). Patients early‐onset (EO) (<30 years) were randomly selected COS study as a control group, North Star Assessment Dysferlinopathy (NSAD) Activity Limitation...
Glioblastoma is the most frequent and aggressive primary brain tumor. Its diagnosis based on resection or biopsy that could be especially difficult dangerous in case of deep location patient comorbidities. Monitoring disease evolution progression also requires repeated biopsies are often not feasible. Therefore, there an urgent need to develop biomarkers diagnose follow glioblastoma a minimally invasive way. In present study, we described novel cancer detection method plasma denaturation...
Abstract Kabuki syndrome (KS, KS1: OMIM 147920 and KS2: 300867) is caused by pathogenic variations in KMT2D or KDM6A . KS characterized multiple congenital anomalies neurodevelopmental disorders. Growth restriction frequently reported. Here we aimed to create specific growth charts for individuals with KS1, identify parameters used size prognosis investigate the impact of hormone therapy on adult height. parental were obtained 95 KS1 (41 females). height, weight, body mass index (BMI)...
Neurotrophins and their receptors control a number of cellular processes, such as survival, gene expression axonal growth, by activating multiple signalling pathways in peripheral neurons. Whether each these controls distinct developmental process remains unknown. Here we describe novel knock-in mouse model expressing chimeric TrkA/TrkC (TrkAC) receptor from TrkA locus. In mice, prospective nociceptors survived, segregated into appropriate peptidergic nonpeptidergic subsets, projected...
GNE myopathy is a rare autosomal recessively inherited muscle disease resulting from mutations in the gene encoding (UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase), key enzyme sialic acid biosynthesis. 154 different pathogenic variants have been previously associated with myopathy.Describe novel large French cohort.We analyzed mutational data 32 index patients. Novel, as well published variants, were examined for possible deleterious effects on splicing.We describe 13 GNE,...
Hereditary myopathies are a group of genetically determined muscle disorders comprising more than 300 entities. In Chile, there no specific registries the distinct forms these myopathies. We now report genetic findings series Chilean patients presenting with limb-girdle weakness unknown etiology. Eighty-two were explored using high-throughput sequencing approaches neuromuscular gene panels, establishing definite diagnosis in 49 (59.8%) and highly probable eight additional cases (9.8%). The...
Abstract Objective Biallelic titin truncating variants (TTNtv) have been associated with a wide phenotypic spectrum, ranging from complex prenatal muscle diseases dysmorphic features to adult‐onset limb‐girdle muscular dystrophy, or without cardiac involvement. Given the size and complexity of TTN, reaching an unequivocal molecular diagnosis precise disease prognosis remains challenging. Methods In this case series, 12 unpublished cases one already published biallelic TTNtv were collected...
Abstract Objective Limb girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous autosomal conditions with some degree phenotypic homogeneity. LGMD is defined as having onset >2 years age progressive proximal weakness, elevated serum creatine kinase levels and dystrophic features on muscle biopsy. Advances in massively parallel sequencing have led to surge genes linked LGMD. Methods The ClinGen Muscular Dystrophies Myopathies gene curation expert panel (MDM GCEP,...