A5069703695- Retinal Development and Disorders
- Retinal Diseases and Treatments
- Genetic Neurodegenerative Diseases
- Connexins and lens biology
- Mitochondrial Function and Pathology
- Cellular transport and secretion
- Parkinson's Disease Mechanisms and Treatments
- RNA regulation and disease
- Advanced biosensing and bioanalysis techniques
- Alzheimer's disease research and treatments
- Cell Adhesion Molecules Research
- Metabolism and Genetic Disorders
- Photoreceptor and optogenetics research
- Glaucoma and retinal disorders
- RNA Research and Splicing
- Neurological disorders and treatments
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Muscle Physiology and Disorders
- Ubiquitin and proteasome pathways
- Neurological diseases and metabolism
- Genomics and Rare Diseases
- CRISPR and Genetic Engineering
- Hearing, Cochlea, Tinnitus, Genetics
- Retinoids in leukemia and cellular processes
- Ocular Oncology and Treatments
Lille Neurosciences & Cognition
2020-2025
Centre de Recherche Jean Pierre Aubert
2011-2025
Université de Lille
2016-2025
Inserm
2016-2025
Centre Hospitalier Universitaire de Lille
2016-2025
Institut de Biologie de Lille
2008-2024
Radboud University Nijmegen
2019-2023
Radboud University Medical Center
2019-2023
Hôpital Roger Salengro
2021
IRCCS Ospedale San Raffaele
2016
PurposeUsing exome sequencing, the underlying variants in many persons with autosomal recessive diseases remain undetected. We explored Stargardt disease (STGD1) as a model to identify missing heritability.MethodsSequencing of ABCA4 was performed 8 STGD1 cases one variant and p.Asn1868Ile trans, 25 variant, 3 no variant. The effect intronic analyzed using vitro splice assays HEK293T cells patient-derived fibroblasts. Antisense oligonucleotides were used correct defects.ResultsIn 24 probands...
The U4 small nuclear RNA (snRNA) forms a duplex with the U6 snRNA and, together U5 and ∼30 proteins, is part of U4/U6.U5 tri-snRNP complex, located at core major spliceosome. Recently, recurrent de novo variants in RNA, transcribed from RNU4-2 gene, least two other RNU genes were discovered to cause neurodevelopmental disorder. We detected inherited heterozygous (n.18_19insA n.56T>C) four out five RNU6 paralogues (n.55_56insG n.56_57insG) 135 individuals 62 families non-syndromic retinitis...
The microtubule-associated protein Tau is mainly expressed in neurons of the CNS and crucial axonal maintenance transport. rationale for as a biomarker neurodegenerative diseases that it major component abnormal intraneuronal aggregates observed numerous tauopathies, including Alzheimer's disease. molecular diversity very useful when analyzing brain or peripheral fluids. Immunohistochemical biochemical characterization allows postmortem classification differential diagnosis tauopathies. As...
Muscleblind-like-1 (MBNL1) is a splicing regulatory factor controlling the fetal-to-adult alternative transitions during vertebrate muscle development. Its capture by nuclear CUG expansions one major cause for type 1 myotonic dystrophy (DM1). Alternative produces MBNL1 isoforms that differ presence or absence of exonic regions 3, 5, and 7. To understand better their respective roles consequences deregulation expression in DM1, here we studied constitutive exons. By combining genetics,...
Purpose Stargardt disease (STGD1) is caused by biallelic mutations in ABCA4, but many patients are genetically unsolved due to insensitive mutation-scanning methods. We aimed develop a cost-effective sequencing method for ABCA4 exons and regions carrying known causal deep-intronic variants. Methods Fifty 12 containing 14 variants of were sequenced using double-tiled single molecule Molecular Inversion Probe (smMIP)-based next-generation sequencing. DNAs 16 STGD1 cases 29 alleles four healthy...
IntroductionPatients with Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD) usually present non-specific progressive chronic kidney disease mild to negative proteinuria and a family history. ADTKD-MUC1 leads the formation of frameshift protein (MUC1fs) that accumulates in cytoplasm, leading tubulo-interstitial damage. prevalence remains unclear as MUC1 variants are not routinely detected by standard NGS techniques.MethodsWe developed bio-informatic counting script can detect...
Biallelic intronic expansions (AAGGG)exp in intron 2 of the RFC1 gene have been shown to be a common cause late-onset ataxia. Since their first description, phenotypes, neurological damage, and pathogenic variants associated with frequently updated. Here, we review various motifs, genetic variants, phenotypes gene. We searched PubMed for scientific articles published between March 1st, 2019, January 15th, 2024. The motifs are highly heterogeneous, making molecular diagnosis clinical...
Abstract Benign hereditary chorea is a rare autosomal dominant disorder presenting with childhood‐onset and slowly progressive chorea. The objective of this study was to describe the clinical genetic features 3 patients who developed Three affected from three generations family benign associated multisystemic basal ganglia, thyroid, lungs, salivary glands, bowels, teeth. TITF‐1 gene screened by microsatellite analysis, sequencing, fluorescence in situ hybridization. Genetic analysis revealed...
Purpose: Inherited retinal dystrophies (IRDs) and inherited optic neuropathies (IONs) are rare diseases defined by specific clinical molecular features. The relative prevalence of these conditions was determined in Southern France.Methods: Patients recruited from a specialized outpatient clinic over 21-year period underwent extensive investigations 107 genes were screened polymerase chain reaction/sequencing.Results: There 1957 IRD cases (1481 families) distributed 70% pigmentary retinopathy...
The goal of this analysis was to determine the test-retest variability functional and structural measures from a cohort patients with advanced forms Stargardt Disease (STGD) participating in SAR422459 (NCT01367444) gene therapy clinical trial.Twenty-two participants, aged 24 66, diagnosed STGD, at least one pathogenic ABCA4 mutation on each chromosome trial, were screened over three visits within 3 weeks or less. Functional visual evaluations included: best-corrected acuity (BCVA) Early...
The mechanisms behind the phenotypic variability and reduced penetrance in autosomal recessive Stargardt disease (STGD1), often a blinding disease, are poorly understood. Identification of unknown modifiers can improve patient family counseling provide valuable information for management.To assess association incompletely penetrant ABCA4 alleles with sex STGD1.Genetic data this cross-sectional study were obtained from 2 multicenter genetic studies 1162 patients clinically suspected STGD1....
Abstract Altered splicing of transcripts, including the insulin receptor (IR) and cardiac troponin (cTNT), is a key feature myotonic dystrophy type I (DM1). CELF MBNL factor members regulate those transcripts. We have previously described an alteration Tau exon 2 in DM1 brain, resulting favored exclusion 2. However, factors required for alternative remain undetermined. Here we report decreased expression family member transcripts brains as assessed by RT‐PCR. By using cellular models with...
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....
Mutations in PRPH2, encoding peripherin-2, are associated with the development of a wide variety inherited retinal diseases (IRDs). To determine causality many PRPH2 variants that have been discovered over last decades, we surveyed all published up to July 2020, describing 720 index patients total carried 245 unique variants. In addition, identified seven novel eight additional patients. The pathogenicity was determined using ACMG guidelines. With this, 107 were classified as pathogenic, 92...