A5029677629- RNA and protein synthesis mechanisms
- Genomics and Rare Diseases
- Hearing, Cochlea, Tinnitus, Genetics
- RNA Research and Splicing
- Genomics and Phylogenetic Studies
- Cystic Fibrosis Research Advances
- RNA modifications and cancer
- Vestibular and auditory disorders
- Genomic variations and chromosomal abnormalities
- RNA regulation and disease
- Neonatal Respiratory Health Research
- Cancer Genomics and Diagnostics
- Retinal Development and Disorders
- Tracheal and airway disorders
- Genomics and Chromatin Dynamics
- Genetic factors in colorectal cancer
- Genetic Neurodegenerative Diseases
- Ion channel regulation and function
- Nutrition, Genetics, and Disease
- Immunodeficiency and Autoimmune Disorders
- Retinal Diseases and Treatments
- Advanced biosensing and bioanalysis techniques
- Connexins and lens biology
- CRISPR and Genetic Engineering
- Genetics and Neurodevelopmental Disorders
Institute for Neurosciences of Montpellier
2021-2025
Inserm
2007-2025
Université de Montpellier
2015-2025
Institut Universitaire de Recherche Clinique
2007-2024
Centre Hospitalier Universitaire de Montpellier
2016-2024
Hôpital Saint Eloi
2021-2024
Institut de Génétique Moléculaire de Montpellier
2011-2023
Physiologie et Médecine Expérimentale du Coeur et des Muscles
2021
Institute for Regenerative Medicine & Biotherapy
2019
Consultative and Diagnostic Center
2019
Non-canonical small open reading frames (sORFs) are among the main regulators of gene expression. The most studied these upstream ORFs (upORFs) located in 5'-untranslated region (UTR) coding genes. Internal (intORFs) sequence and downstream (dORFs) 3'UTR have received less attention. Different bioinformatics tools permit prediction single nucleotide variants (SNVs) altering upORFs, mainly those creating AUGs or deleting stop codons, but no tool predicts non-canonical translation initiation...
USH2A sequencing in three affected members of a large family, referred for the recessive USH2 syndrome, identified single pathogenic alteration one them and different mutation two nieces. As patients carried common haplotype, they likely shared not found by standard techniques. Analysis RNA from nasal cells individual an additional pseudoexon (PE) resulting deep intronic mutation. This was confirmed minigene assay. is first example Usher syndrome (USH) with causing activation PE. The finding...
Deep intronic mutations leading to pseudoexon (PE) insertions are underestimated and most of these splicing alterations have been identified by transcript analysis, for instance, the first deep mutation in USH2A, gene frequently involved Usher syndrome type II (USH2). Unfortunately, analyzing USH2A transcripts is challenging 1.8%-19% USH2 individuals carrying a single recessive mutation, second yet be identified. We developed validated DNA next-generation sequencing approach identify...
Abstract Enrichment capture methods for NGS are widely used, however, they evolve rapidly and it is necessary to periodically measure their strengths weaknesses before transfer diagnostic services. We assessed two recently released custom DNA solution-capture enrichment NGS, namely Illumina NRCCE Agilent SureSelect QXT , against a reference method NimbleGen SeqCap EZ Choice on similar gene panel, sharing 678 kb 110 genes. Two MiSeq runs of 12 samples each have been performed, the three...
Most of the 2,000 variants identified in CFTR (cystic fibrosis transmembrane regulator) gene are rare or private. Their interpretation is hampered by lack available data and resources, making patient care genetic counseling challenging. We developed a patient-based database dedicated to annotations context their cis- trans-allelic combinations. Based on almost 30 years experience testing, CFTR-France (https://cftr.iurc.montp.inserm.fr/cftr) currently compiles 16,819 variant records from...
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...
Inherited retinal dystrophies (IRDs) are characterized by progressive photoreceptor degeneration and vision loss. Usher syndrome (USH) is a syndromic IRD retinitis pigmentosa (RP) hearing USH clinically genetically heterogeneous, the most prevalent causative gene USH2A. USH2A mutations also account for large number of isolated autosomal recessive RP (arRP) cases. This high prevalence due to two recurrent mutations, c.2276G>T c.2299delG. Due size cDNA, augmentation therapy inaccessible....
MobiDetails is an expert tool, online application which gathers useful data for the interpretation of DNA variants in context molecular diagnosis. It brings together a single tool many sources data, such as population genetics, various kinds predictors, Human Genome Variation Society (HGVS) nomenclatures, curated databases, and access to annotations. Accurate crucial can impact patient care or have familial outcomes (prenatal diagnosis). Its importance will increase coming years with...
Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is an inherited late-onset neurological disease caused by bi-allelic AAGGG pentanucleotide expansions within intron 2 of RFC1. Despite extensive studies, the pathophysiological mechanism these intronic remains elusive. We screened clinical exome sequencing two unrelated patients presenting with ataxia. A repeat-primer polymerase chain reaction was used for RFC1 expansion identification. mRNA expression assessed...
The usherin gene (USH2A) has been screened for mutations causing Usher syndrome type II (USH2). Two protein isoforms have identified: a short isoform of 1,546 amino acids and more recently recognized extending to 5,202 acids. We the full length by genomic sequencing. confirm that many occur in exons contributing solely longer form. USH2 is an autosomal recessive disorder and, contrast previous studies, both were identified 23 patients single mutation 2 out 33 patients. A total 34 distinct...
Alterations of USH2A, encoding usherin, are responsible for more than 70% cases Usher syndrome type II (USH2), a recessive disorder that combines moderate to severe hearing loss and retinal degeneration. The longest USH2A transcript encodes usherin isoform b, 5,202-amino-acid transmembrane protein with an exceptionally large extracellular domain consisting notably Laminin N-terminal numerous EGF-like (LE) Fibronectin III (FN3) repeats. Mutations scattered throughout the gene mostly private....
We have systematically analyzed the two known minor genes involved in Usher syndrome type 2, DFNB31 and GPR98, for mutations a cohort of 31 patients not linked to USH2A. PDZD7, an 2 (USH2) related gene, was when indicated. found that GPR98 contribute significantly USH2. report 17 10 individuals, doubling number reported date. In contrast usherin, mutational spectrum predominantly results truncated protein product. This is true even mutation affects splicing, we incorporated splicing reporter...
The SLC12 gene family consists of SLC12A1-SLC12A9, encoding electroneutral cation-coupled chloride co-transporters. SCL12A2 has been shown to play a role in corticogenesis and therefore represents strong candidate neurodevelopmental disorder gene. Through trio exome sequencing we identified de novo mutations SLC12A2 six children with disorders. All had developmental delay or intellectual disability ranging from mild severe. Two sensorineural deafness. We also variants three individuals...
We show that massively parallel targeted sequencing of 19 genes provides a new and reliable strategy for molecular diagnosis Usher syndrome (USH) nonsyndromic deafness, particularly appropriate these disorders characterized by high clinical genetic heterogeneity complex structure several the involved. A series 71 patients including previously screened Sanger plus newly referred was studied. Ninety-eight percent variants identified were found next-generation (NGS). NGS proved to be efficient...
The purpose of this study was to establish the mutation spectrum an Usher type I cohort 61 patients from France and describe a diagnostic strategy, including strategy for estimating pathogenicity sequence changes.To optimize identification (USH)-causative mutations, taking into account genetic heterogeneity, preliminary haplotyping at five USH1 loci performed prioritize gene be sequenced, as previously described. Coding exons flanking intronic sequences were sequenced and, where necessary,...
Using the Universal Mutation Database (UMD) software, we have constructed "UMD-USHbases", a set of relational databases nucleotide variations for seven genes involved in Usher syndrome (MYO7A, CDH23, PCDH15, USH1C, USH1G, USH3A and USH2A). Mutations type I causing are also recorded non-syndromic hearing loss cases mutations USH2A retinitis pigmentosa. provides particular challenge molecular diagnostics because clinical heterogeneity. As many missense changes, all contain apparently...
Molecular diagnosis in Usher syndrome type 1 and 2 patients led to the identification of 21 sequence variations located noncanonical positions splice sites MYO7A, CDH23, USH1C, USH2A genes. To establish experimentally splicing pattern these substitutions, whose impact on is not always predictable by available softwares, ex vivo assays were performed. The branch-point mapping strategy was also used investigate further a putative mutation intron 43. Aberrant demonstrated for 16 (76.2%) tested...
Bilateral sensorineural hearing loss (HL), classically described as mild to severe with a typically down-sloping audiometric configuration, is the earliest symptom occurring in Usher syndrome type II (USH2). Audiological findings were analyzed total of 100 USH2 patients (92 families) divided into three groups according gene involved: 88 USH2A, 10 GPR98 and 2 DFNB31 patients. A fine analysis audiograms was performed (pure tone average, degree severity, configuration). The median age HL...
Inherited retinal dystrophies (IRDs) are caused by mutations in over 200 genes, resulting a range of therapeutic options. Translational read-through inducing drugs (TRIDs) offer the possibility treating multiple IRDs regardless causative gene. TRIDs promote ribosomal misreading premature stop codons, which results incorporation near-cognate amino acid to produce full-length protein. The IRD choroideremia (CHM) is pertinent candidate for TRID therapy, as nonsense variants cause 30% cases....
Molecular diagnosis of cystic fibrosis and transmembrane regulator (CFTR)-related disorders led to the worldwide identification nearly 1,900 sequence variations in CFTR gene that consist mainly private point mutations small insertions/deletions. Establishing their effect on function encoded protein therefore involvement disease is still challenging directly impacts genetic counseling. In this context, we built a decision tree following international guidelines for classification variants...
We have shown that nasal ciliated epithelium, which can be easily biopsied under local anesthetic, provides a good source of RNA transcripts from eight the nine known genes cause Usher syndrome, namely, MYO7A, USH1C, CDH23, PCDH15, USH1G for type 1, and USH2A, GPR98, WHRN 2. Furthermore, or predicted effect on mRNA splicing variants was faithfully reproduced in sample as measured by nested RT-PCR. These included changes at canonical acceptor site, within noncanonical site both synonymous...