A5078358993- Retinal Development and Disorders
- Retinal Diseases and Treatments
- Photoreceptor and optogenetics research
- Cellular transport and secretion
- Parkinson's Disease Mechanisms and Treatments
- RNA regulation and disease
- Neurological diseases and metabolism
- Lysosomal Storage Disorders Research
- Mitochondrial Function and Pathology
- Pluripotent Stem Cells Research
- Genetics and Neurodevelopmental Disorders
- Glaucoma and retinal disorders
- Carbohydrate Chemistry and Synthesis
- Retinal and Macular Surgery
- Genomics and Rare Diseases
- CRISPR and Genetic Engineering
- Muscle Physiology and Disorders
- Genetic and Kidney Cyst Diseases
- Ubiquitin and proteasome pathways
- Neurobiology and Insect Physiology Research
- Cerebrovascular and genetic disorders
- Nuclear Receptors and Signaling
- Retinal and Optic Conditions
- Banana Cultivation and Research
- Advanced biosensing and bioanalysis techniques
Institut de la Vision
2016-2025
Centre National de la Recherche Scientifique
2016-2025
Inserm
2016-2025
Sorbonne Université
2016-2025
Pitié-Salpêtrière Hospital
2009-2018
Institut du Cerveau
2010-2018
Assistance Publique – Hôpitaux de Paris
2011-2018
Sorbonne Paris Cité
2018
University College London
2015
National Institute on Aging
2015
Recent studies indicate an increased frequency of mutations in the gene encoding glucocerebrosidase (GBA), a deficiency which causes Gaucher's disease, among patients with Parkinson's disease. We aimed to ascertain GBA ethnically diverse group disease.Sixteen centers participated our international, collaborative study: five from Americas, six Europe, two Israel, and three Asia. Each center genotyped standard DNA panel permit comparison genotyping results across centers. Genotypes phenotypic...
Pathogenic variants in the glucocerebrosidase gene (GBA) encoding enzyme deficient Gaucher's disease (GD) are associated with Parkinson's (PD). To investigate sequence variants, their association PD and related phenotypes a large cohort of European, mostly French, patients controls, we sequenced all exons GBA 786 from 525 unrelated multiplex families, 605 apparently sporadic 391 ethnically matched controls. mutations were significantly more frequent (odds ratio=6.98, 95% confidence interval...
<h3>Objective:</h3> Glucocerebrosidase (<i>GBA</i>) gene mutations represent a strong risk factor for Parkinson disease (PD). PD penetrance in <i>GBA</i> mutation carriers, which represents key issue genetic counseling, especially relatives of patients with Gaucher (GD), is unknown. Our objective was to estimate familial study carriers. <h3>Methods:</h3> Probands were recruited through the French Disease Genetic Study Group. All exons sequenced probands and their relatives. To age-specific...
The recently identified C9orf72 gene accounts for a large proportion of amyotrophic lateral sclerosis and frontotemporal lobar degenerations. As several forms these disorders are associated with parkinsonism, we hypothesized that some patients Parkinson's disease or other parkinsonism might carry pathogenic expansions. Therefore, looked repeat expansions in 1446 unrelated parkinsonian consisting 1225 clinically diagnosed disease, 123 progressive supranuclear palsy, 21 corticobasal...
Cone and cone-rod dystrophies are clinically genetically heterogeneous inherited retinal disorders with predominant cone impairment. They should be distinguished from the more common group of rod-cone (retinitis pigmentosa) due to their severe visual prognosis early central vision loss. The purpose our study was document mutation spectrum a large French cohort dystrophies.We applied Next-Generation Sequencing targeting panel 123 genes implicated in diseases 96 patients. A systematic...
Progressive inherited retinal degenerations (IRDs) affecting rods and cones are clinically genetically heterogeneous can lead to blindness with limited therapeutic options. The major gene defects have been identified in subjects of European Asian descent only few reports North African descent. Genome, targeted next-generation, Sanger sequencing was applied cohort ∼4000 IRDs cases. Expression analyses were performed including Chip-seq database analyses, on human-derived organoids (ROs),...
Rab proteins are small molecular weight guanosine triphosphatases involved in the regulation of vesicular trafficking.1 Three 4 X-linked RAB genes specific to brain, including RAB39B . Recently, Wilson et al.2 reported that mutations cause intellectual disability (ID) and pathologically confirmed Parkinson disease (PD). They identified a ∼45-kb deletion resulting complete loss an Australian kindred missense mutation large Wisconsin kindred. Here, we report additional affected man with...
To describe the clinical outcome and late-stage findings of extensive macular atrophy with pseudodrusen-like appearance (EMAP).
Since Next Generation DNA Sequencing (NGS) was first used to study Miller syndrome,[1][1] exome capture and sequencing have uncovered novel causative mutations in an increasing number of genetic disorders, including neurodegenerative diseases.[2][2],[–][3],[4][4] Two independent groups recently
Mutations in LRIT3, coding for a Leucine-Rich Repeat, immunoglobulin-like and transmembrane domains 3 protein lead to autosomal recessive complete congenital stationary night blindness (cCSNB). The role of the corresponding ON-bipolar cell signaling cascade remains be elucidated. Here we genetically functionally characterize commercially available Lrit3 knock-out mouse, model study function pathogenic mechanism LRIT3. We confirm that insertion Bgeo/Puro cassette allele introduces premature...
Biallelic variants in CLN3 lead to a spectrum of diseases, ranging from severe neurodegeneration with retinal involvement (juvenile neuronal ceroid lipofuscinosis) retina-restricted conditions. To provide detailed description the phenotype patients isolated degeneration harboring biallelic pathogenic and attempt phenotype-genotype correlation associated this gene defect. This retrospective cohort study included carrying extracted inherited disorders (IRDs) investigated at National Reference...
Mutations in the leucine-rich-repeat kinase 2 (LRRK2) gene have been identified families with autosomal dominant Parkinson's disease (PD) and sporadic cases; G2019S mutation is single most frequent. Intriguingly, frequency of this PD patients varies greatly among ethnic groups geographic origins: it present at <0.1% East Asia, ∼2% European-descent can reach frequencies up to 15–40% Ashkenazi Jews North African Arabs. To ascertain evolutionary dynamics different populations, we genotyped 74...
Pathogenic variants in RP1L1 are associated with autosomal dominant occult macular dystrophy (OMD) and recessive retinitis pigmentosa (RP). In this study, we investigated the phenotypic genotypic landscape of RP1L1-associated retinopathy an ethnically heterogeneous cohort. This multicenter cohort study retrospectively collected following data: best-corrected visual acuity (BCVA), color fundus photograph (CFP), optical coherence tomography (OCT), short-wavelength autofluorescence (SW-AF),...
The purpose of this study was to describe the mutational landscape, clinical characteristics, and natural history PCARE-associated retinopathy. Retrospective cohort including 28 patients (56 eyes) affected by an inherited retinal disease related PCARE variants. main outcome measures were best-corrected visual acuity (BCVA) degree vision impairment, kinetic field (KVF) area delimited with V4e target, macular atrophy (MA) definitely decreased autofluorescence (DDAF) on short-wavelength...
Heterozygous mutations in the glucocerebrosidase gene ( GBA ) encoding enzyme deficient Gaucher disease (GD), an autosomal recessive lysosomal storage disease, are most common risk factors for parkinsonism several populations. A large meta-analysis, pooling genotyping data from 16 different centers United States, Europe, Israel, and Asia, yielded a combined odds ratio (OR) subjects with Parkinson (PD) of >51 but did not include North Africans. Ashkenazi Jewish patients PD had highest...
Although accumulating data indicate that increased α-synuclein expression is crucial for Parkinson disease (PD), mechanisms regulating the transcription of its gene, SNCA, are largely unknown. Here, we describe a pathway expression. Our show ZSCAN21 stimulates SNCA in neuronal cells and TRIM41 an E3 ubiquitin ligase ZSCAN21. In contrast, TRIM17 decreases TRIM41-mediated degradation Silencing consistently reduces expression, whereas knockdown increases it. The mRNA levels TRIM17, ZSCAN21,...
<h3>Importance</h3> A precise phenotypic characterization of retinal dystrophies is needed for disease modeling as a basis future therapeutic interventions. <h3>Objective</h3> To compare genotype, phenotype, and structural changes in patients with rod-cone dystrophy (RCD) associated mutations in<i>PDE6A</i>or<i>PDE6B</i>. <h3>Design, Setting, Participants</h3> In retrospective cohort study conducted Paris, France, from January 2007 to September 2017, 54 1095 index RCD underwent clinical...
We investigated the prevalence of reported deep-intronic variants in a French cohort 70 patients with Stargardt disease harboring monoallelic pathogenic variant on exonic regions ABCA4. Direct Sanger sequencing selected intronic ABCA4 was conducted. Complete phenotypic analysis and correlation genotype performed case known identified. All other found analyzed sequences were queried for minor allele frequency possible pathogenicity by silico predictions. The second mutated 14 (20%) subjects....
To investigate the clinical, functional, and imaging characteristics in patients affected by inherited retinal diseases associated with RDH5 RLBP1 gene variants, to report novel genotype-phenotype correlations.
Abstract Juvenile polyposis syndrome is a hamartomatous intestinal associated with malignant changes in 20% of patients at an early age. Germline mutations mostly involve two genes, SMAD4 and BMPR1 , no strong evidence phenotype‐genotype correlation, which could be predictive the specific long‐term evolution. In contrast, PTEN are more commonly Cowden related diseases. Forty‐two unrelated affected by juvenile were analyzed for germline alterations BMPR1A clinical histological features....