Mathilde Nizon
A5037487892- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Congenital heart defects research
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- Connective tissue disorders research
- Fetal and Pediatric Neurological Disorders
- RNA regulation and disease
- Epigenetics and DNA Methylation
- Prenatal Screening and Diagnostics
- Immunodeficiency and Autoimmune Disorders
- Genetic Syndromes and Imprinting
- Microtubule and mitosis dynamics
- Genetic and Kidney Cyst Diseases
- Chromatin Remodeling and Cancer
- Genomics and Chromatin Dynamics
- Cellular transport and secretion
- Cell Adhesion Molecules Research
- Hereditary Neurological Disorders
- Metabolism and Genetic Disorders
- Neurogenetic and Muscular Disorders Research
- Peptidase Inhibition and Analysis
- Hedgehog Signaling Pathway Studies
Nantes Université
2018-2025
Inserm
2012-2025
Génétique Médicale & Génomique Fonctionelle
2017-2025
Centre Hospitalier Universitaire de Nantes
2017-2025
Centre National de la Recherche Scientifique
2018-2025
Institut du Thorax
2018-2025
University of Zurich
2023
Institut des Maladies Génétiques Imagine
2015-2023
Université de Bourgogne
2023
Collaborative Group (United States)
2023
PurposeTo assess the contribution of rare variants in genetic background toward variability neurodevelopmental phenotypes individuals with copy-number (CNVs) and gene-disruptive variants.MethodsWe analyzed quantitative clinical information, exome sequencing, microarray data from 757 probands 233 parents siblings who carry disease-associated variants.ResultsThe number likely deleterious functionally intolerant genes (“other hits”) correlated expression 16p12.1 deletion (n=23, p=0.004) autism...
Abstract We report detailed functional analyses and genotype-phenotype correlations in 392 individuals carrying disease-causing variants SCN8A, encoding the voltage-gated Na+ channel Nav1.6, with aim of describing clinical phenotypes related to effects. Six different subgroups were identified: Group 1, benign familial infantile epilepsy (n = 15, normal cognition, treatable seizures); 2, intermediate 33, mild intellectual disability, partially pharmaco-responsive); 3, developmental epileptic...
Abstract Dystonia is a rare-disease trait for which large-scale genomic investigations are still underrepresented. Genetic heterogeneity among patients with unexplained dystonia warrants interrogation of entire genome sequences, but this has not yet been systematically evaluated. To significantly enhance our understanding the genetic contribution to dystonia, we (re)analyzed 2,874 whole-exome sequencing (WES), 564 whole-genome (WGS), as well 80 fibroblast-derived proteomics datasets,...
Abstract GRIN-related disorders are rare developmental encephalopathies with variable manifestations and limited therapeutic options. Here, we present the first non-randomized, open-label, single-arm trial (NCT04646447) designed to evaluate tolerability efficacy of L-serine in children GRIN genetic variants leading loss-of-function. In this phase 2A trial, patients aged 2–18 years loss-of-function pathogenic received for 52 weeks. Primary end points included safety by measuring changes...
Abstract Background Classical organic acidurias including methylmalonic aciduria (MMA), propionic (PA) and isovaleric (IVA) are severe inborn errors of the catabolism branched-chain amino acids odd-numbered chain fatty acids, presenting with complications. Methods This study investigated long-term outcome 80 patients classical (38 MMA, 24 PA 18 IVA) by integrating clinical, radiological, biochemical genetic data. Results Patients were followed-up for a mean 14 years [age 3.3-46.3 years]....
Abstract Hearing loss is the most common sensory disorder and because of its high genetic heterogeneity, implementation Massively Parallel Sequencing (MPS) in diagnostic laboratories greatly improving possibilities offering optimal care to patients. We present results a two-year period molecular diagnosis that included 207 French families referred for non-syndromic hearing loss. Our multi-step strategy involved (i) DFNB1 locus analysis, (ii) MPS 74 genes, (iii) additional approaches...
Background Arthrogryposis multiplex congenita (AMC) is characterised by congenital joint contractures in two or more body areas. AMC exhibits wide phenotypic and genetic heterogeneity. Our goals were to improve the diagnosis rates of AMC, evaluate added value whole exome sequencing (WES) compared with targeted (TES) identify new genes 315 unrelated undiagnosed families. Methods Several genomic approaches used including mapping disease loci consanguineous families, TES then WES. Sanger was...
Germline loss-of-function variants in CTNNB1 cause neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV; OMIM 615075) are the most frequent, recurrent monogenic of cerebral palsy (CP). We investigated range clinical phenotypes owing to disruptions determine association between NEDSDV CP.Genetic information from 404 individuals collectively 392 pathogenic were ascertained for study. From these, detailed 52 previously unpublished collected combined 68 published...
Incomplete penetrance is observed for most monogenic diseases. However, neurodevelopmental disorders, the interpretation of single and multi-nucleotide variants (SNV/MNVs) usually based on paradigm complete penetrance. From 2020 to 2022, we proposed a collaboration study with French molecular diagnosis intellectual disability network. The aim was recruit families whom index case, diagnosed disorder, carrying pathogenic or likely variant an OMIM morbid gene inherited from asymptomatic parent....
Autosomal recessive microcephaly or primary hereditary (MCPH) is a genetically heterogeneous neurodevelopmental disorder characterized by reduction in brain volume, indirectly measured an occipitofrontal circumference (OFC) 2 standard deviations more below the age- and sex-matched mean (-2SD) at birth -3SD after 6 months, leading to intellectual disability of variable severity. The abnormal spindle-like gene (ASPM), human ortholog Drosophila melanogaster "abnormal spindle" (asp), encodes...
To provide new insights into the FOXG1-related clinical and imaging phenotypes refine phenotype-genotype correlation in FOXG1 syndrome.We analyzed of a cohort 45 patients with pathogenic or likely variant performed correlations.A total 37 different heterozygous mutations were identified, which 18 are novel. We described broad spectrum neurodevelopmental phenotypes, characterized by severe postnatal microcephaly developmental delay accompanied hyperkinetic movement disorder, stereotypes sleep...
The Xq28 duplication involving the MECP2 gene (MECP2 duplication) has been mainly described in male patients with severe developmental delay (DD) associated spasticity, stereotypic movements and recurrent infections. Nevertheless, only a few series have published. We aimed to better describe phenotype of this condition, focus on morphological neurological features. Through national collaborative study, we report large French 59 affected males interstitial duplication. Most (93%) shared...
Abstract Variants of uncertain significance (VUS) are a significant issue for the molecular diagnosis rare diseases. The publication episignatures as effective biomarkers certain Mendelian neurodevelopmental disorders has raised hopes to help classify VUS. However, prediction abilities most published have not been independently investigated yet, which is prerequisite an informed and rigorous use in diagnostic setting. We generated DNA methylation data from 101 carriers (likely) pathogenic...
Neurodevelopmental disorders with intellectual disability (ND/ID) are a heterogeneous group of diseases driving lifelong deficits in cognition and behavior no definitive cure. X-linked disorder 105 (XLID105, #300984; OMIM) is ND/ID driven by hemizygous variants the