A5065858723- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Metabolism and Genetic Disorders
- Genetic Neurodegenerative Diseases
- Hereditary Neurological Disorders
- Protein Tyrosine Phosphatases
- Machine Learning in Bioinformatics
- Genomics and Rare Diseases
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Dermatological and Skeletal Disorders
- Cell Image Analysis Techniques
- Retinal Development and Disorders
- Genetic Syndromes and Imprinting
- Nuclear Structure and Function
- Cell death mechanisms and regulation
- Biomedical Text Mining and Ontologies
- Acute Myeloid Leukemia Research
- Bioinformatics and Genomic Networks
- Autophagy in Disease and Therapy
- Neurological diseases and metabolism
- Neuroinflammation and Neurodegeneration Mechanisms
- Multiple Myeloma Research and Treatments
- Connexins and lens biology
- Cerebrovascular and genetic disorders
UiT The Arctic University of Norway
2023-2025
University of Oslo
2025
Inserm
2014-2024
Université d'Angers
2014-2024
Centre National de la Recherche Scientifique
2013-2024
Baylor College of Medicine
2021
Houston Methodist
2021
Methodist Hospital
2021
Singapore National Eye Center
2021
Singapore Eye Research Institute
2021
Abstract Objective Mutations of the mitofusin 2 gene (MFN2) may account for at least a third cases Charcot–Marie–Tooth disease type (CMT2). This study investigates mitochondrial cellular bioenergetics in MFN2 ‐related CMT2A. Methods Mitochondrial network morphology and metabolism were studied cultures skin fibroblasts obtained from four CMT2A patients harboring novel missense mutations gene. Results Although appeared morphologically unaltered, there was significant defect coupling associated...
<h3>Abstract</h3> <h3>Background</h3> Mitochondrial DNA (mtDNA) diseases are rare disorders whose prevalence is estimated around 1 in 5000. Patients usually tested only for deletions and common mutations of mtDNA which account 5–40% cases, depending on the study. However, not known. <h3>Methods</h3> We analysed whole a cohort 743 patients suspected manifesting mitochondrial disease, after excluding mutations. Both heteroplasmic homoplasmic variants were identified using two complementary...
Abstract Here we explored the role of interleukin-1β (IL-1β) repressor cytokine, IL-1 receptor antagonist (IL-1rn), in both healthy and abnormal hematopoiesis. Low IL-1RN is frequent acute myeloid leukemia (AML) patients represents a prognostic marker reduced survival. Treatments with IL-1β monoclonal antibody canakinumab reduce expansion leukemic cells, including CD34 + progenitors, AML xenografts. In vivo deletion IL-1rn induces hematopoietic stem cell (HSC) differentiation into lineage...
Abstract Hereditary optic neuropathies are heterogeneous diseases characterized by the degeneration of retinal ganglion cells leading to nerve atrophy and impairment central vision. We found a common coupling defect oxidative phosphorylation in fibroblasts patients affected autosomal dominant (mutations OPA1 ), associated with cataract OPA3 Leber's hereditary neuropathy, disorder point mutations mitochondrial DNA complex I genes. Interestingly, energetic was significantly more pronounced...
Autosomal dominant optic atrophy (ADOA), also known as Kjer disease, is characterized by moderate to severe loss of visual acuity with an insidious onset in early childhood, blue-yellow dyschromatopsia, and central scotoma. An gene, called OPA1, has been identified most cases the disease. A total 83 OPA1 mutations, often family-specific, have reported so far, observations support hypothesis that haploinsufficiency functional a single allele may lead ADOA. We developed new locus-specific...
Abstract Background The dysfunction of OPA1, a dynamin GTPase involved in mitochondrial fusion, is responsible for large spectrum neurological disorders, each which includes optic neuropathy. database dedicated to OPA1 ( https://www.lovd.nl/OPA1 ), created 2005 , has now evolved towards centralized and more reliable using the Global Variome shared Leiden Open-source Variation Database (LOVD) installation. Results updated database, registers all patients from our center as well those reported...
Hereditary optic neuropathies are caused by the degeneration of retinal ganglion cells whose axons form nerves, with a consistent genetic heterogeneity. As part our diagnostic activity, we retrospectively evaluated combination Leber hereditary neuropathy mutations testing exon sequencing 87 nuclear genes on 2186 patients referred for suspected neuropathies. The positive diagnosis rate in individuals was 18% (199/1126 index cases), 92% (184/199) carrying one three main pathogenic variants...
Leber's hereditary optic neuropathy (LHON) is caused by mutations in the complex I subunits of respiratory chain. Although patients have been treated with idebenone since 1992, efficacy drug still a matter debate.We evaluated effect fibroblasts from LHON using enzymatic and polarographic measurements.Complex activity was 42% greater compared to controls (p = 0.002). Despite this improvement, effects on mitochondrial respiration were contradictory, leading impairment some cases stimulation...
Autosomal-dominant optic atrophy (ADOA) is the most common inherited neuropathy, due to mutations in 1 gene (OPA1) about 60%-80% of cases. At present, clinical heterogeneity patients carrying OPA1 variants renders genotype-phenotype correlations difficulty. Since 2005, when we published first locus-specific database (LSDB) dedicated OPA1, a large amount new and genetic knowledge has emerged, prompting us update this database. We have used Leiden Open-Source Variation Database develop...
Leber's hereditary optic neuropathy (MIM#535000), the commonest mitochondrial DNA-related disease, is caused by mutations affecting complex I. The clinical expression of disorder, usually occurring in young adults, typically characterized subacute, sequential, bilateral visual loss, resulting from degeneration retinal ganglion cells. As precise action DNA on overall cell metabolism unknown, we investigated metabolomic profile disease. High performance liquid chromatography coupled with...
Abstract Optic Atrophy 1 ( OPA 1) gene mutations cause diseases ranging from isolated dominant optic atrophy DOA ) to various multisystemic disorders. 1, a large GTP ase belonging the dynamin family, is involved in mitochondrial network dynamics. The majority of encodes truncated forms protein and causes through haploinsufficiency, whereas missense are predicted disease deleterious dominant‐negative mechanisms. We used 3D imaging biochemical analysis explore autophagy mitophagy fibroblasts...
Biallelic mutations in ACO2, encoding the mitochondrial aconitase 2, have been identified individuals with neurodegenerative syndromes, including infantile cerebellar retinal degeneration and recessive optic neuropathies (locus OPA9). By screening European cohorts of genetically unsolved inherited neuropathies, we 61 cases harbouring variants among whom 50 carried dominant mutations, emphasizing for first time important contribution ACO2 monoallelic pathogenic to atrophy. Analysis...
To determine the plasma metabolomic profile of exudative age-related macular degeneration (AMD), we performed a targeted metabolomics study on from patients (n = 40, mean age 81.1) compared to an age- and sex-matched control group 81.8). All included had documented AMD, causing significant visual loss (mean logMAR acuity 0.63), group. Patients controls did not differ in terms body mass index co-morbidities. Among 188 metabolites analyzed, 150 (79.8%) were accurately measured. The...
Serum protein electrophoresis (SPE) is a common clinical laboratory test, mainly indicated for the diagnosis and follow-up of monoclonal gammopathies. A time-consuming potentially subjective human expertise required SPE analysis to detect possible pitfalls provide clinically relevant interpretation.An expert-annotated dataset 159 969 entries was used develop SPECTR (serum computer-assisted recognition), deep learning-based artificial intelligence, which analyzes interprets raw curves...