A5080418392- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Neurological disorders and treatments
- Parkinson's Disease Mechanisms and Treatments
- DNA Repair Mechanisms
- Genetics and Neurodevelopmental Disorders
- Endoplasmic Reticulum Stress and Disease
- Metabolism and Genetic Disorders
- Genomics and Rare Diseases
- Hereditary Neurological Disorders
- Neuroscience and Neuropharmacology Research
- Epilepsy research and treatment
- Genetic Associations and Epidemiology
- Genomic variations and chromosomal abnormalities
- Neurological diseases and metabolism
- Botulinum Toxin and Related Neurological Disorders
- Glycogen Storage Diseases and Myoclonus
- Ion channel regulation and function
- RNA modifications and cancer
- Lysosomal Storage Disorders Research
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Amyotrophic Lateral Sclerosis Research
- RNA regulation and disease
- Ubiquitin and proteasome pathways
McGill University
1998-2025
Université Libre de Bruxelles
2015-2024
Erasmus Hospital
2014-2023
Max Delbrück Center
2023
Charité - Universitätsmedizin Berlin
2023
RWTH Aachen University
2018-2022
Forschungszentrum Jülich
2022
University of Utah
1997-2021
University of Chicago Medical Center
2017-2021
Mayo Clinic in Arizona
2021
Friedreich's ataxia (FRDA) is an autosomal recessive, degenerative disease that involves the central and peripheral nervous systems heart. A gene, X25 , was identified in critical region for FRDA locus on chromosome 9q13. The gene encodes a 210-amino acid protein, frataxin, has homologs distant species such as Caenorhabditis elegans yeast. few patients were found to have point mutations but majority homozygous unstable GAA trinucleotide expansion first intron.
The gene responsible for Friedreich's ataxia, a disease characterized by neurodegeneration and cardiomyopathy, has recently been cloned its product designated frataxin. A in Saccharomyces cerevisiae was whose predicted protein high sequence similarity to the human frataxin protein. yeast (yeast homolog, YFH1) encodes mitochondrial involved iron homeostasis respiratory function. Human also shown be Characterizing mechanism which YFH1 regulates may help define pathologic process leading cell...
Carbamazepine causes various forms of hypersensitivity reactions, ranging from maculopapular exanthema to severe blistering reactions. The HLA-B*1502 allele has been shown be strongly correlated with carbamazepine-induced Stevens–Johnson syndrome and toxic epidermal necrolysis (SJS–TEN) in the Han Chinese other Asian populations but not European populations.
Friedreich ataxia is a progressive neurodegenerative disorder caused by loss of function mutations in the frataxin gene. In order to unravel we developed monoclonal antibodies raised against different regions protein. These detect processed 18 kDa protein various human and mouse tissues cell lines that severely reduced patients. By immunocytofluorescence immunocytoelectron microscopy show located mitochondria, associated with mitochondrial membranes crests. Analysis cellular localization...
In the late 1800s, Nikolaus Friedreich first described "degenerative atrophy of posterior columns spinal cord," noting its connection to progressive ataxia, sensory loss, and muscle weakness, now recognized as ataxia (FRDA). Renewed interest in disease 1970s 80s by Quebec Cooperative Group Anita Harding led development clinical diagnostic criteria insights into associated biochemical abnormalities, although primary defect remained unknown. 1988, Susan Chamberlain mapped FRDA's location on...
Friedreich's ataxia is the most common inherited ataxia. Ninety-six percent of patients are homozygous for GAA trinucleotide repeat expansions in first intron frataxin gene. The remaining cases compound heterozygotes a expansion and point mutation. We report here identification 10 novel mutations, detection previously described mutation (G130V) two additional families. Most truncating mutations were exon 1. All missense last three exons coding mature protein. clinical features 25 with...
Friedreich ataxia (FRDA) is associated with the expansion of a GAA. TTC triplet repeat in first intron frataxin gene, resulting reduced levels mRNA and protein. To investigate mechanisms by which intronic produces its effect, GAA.TTC repeats various lengths (9 to 270 triplets) were cloned both orientations reporter gene. Plasmids containing these transiently transfected into COS-7 cells. A length- orientation-dependent inhibition gene expression was observed. RNase protection Northern blot...
We studied genotype-phenotype correlations in a group of 100 patients with typical Friedreich ataxia (FRDA), and three groups atypical clinical presentations, including 44 Acadian FRDA, 8 late-onset FRDA (LOFA), 6 retained reflexes (FARR). All patients, except 3 carried two copies the FRDA-associated GAA triplet repeat expansion. Overall, phenotypic spectrum appeared to be wider than defined by currently used diagnostic criteria. Our study indicated existence several sources variability...
Deletions at 16p13.11 are associated with schizophrenia, mental retardation, and most recently idiopathic generalized epilepsy. To evaluate the role of deletions, as well other structural variation, in epilepsy disorders, we used genome-wide screens to identify copy number variation 3812 patients a diverse spectrum syndromes 1299 neurologically-normal controls. Large deletions (> 100 kb) were observed 23 patients, whereas no control had deletion greater than 16 kb. Patients, even those...
Glutamic acid decarboxylase (GAD) catalyzes the conversion of glutamic into GABA. GAD autoantibodies (GAD-Ab) have been described in diabetes mellitus and diseases involving central nervous system such as stiff-person syndrome cerebellar ataxia. However, pathogenic role GAD-Ab neurological remains a matter debate. Using neurophysiological neurochemical methods, we analyzed effects intracerebellar paraspinal administration rats. Intracerebellar IgG from patients with involvement (IgG-GAD)...
To determine the incidence of spinocerebellar ataxia (SCA) types 1, 2, 3, 6, and 7 Friedreich's (FA) among a large panel families.The ataxias are clinically genetically heterogeneous group neurodegenerative diseases that variably affect cerebellum, brainstem, tracts. Trinucleotide repeat expansions have been shown to be mutational mechanism for five dominantly inherited SCAs as well FA.We collected DNA samples clinical data from patients representing 361 families with adult-onset unknown...
BackgroundFriedreich ataxia, an autosomal recessive neurodegenerative and cardiac disease, is caused by abnormally low levels of frataxin, essential mitochondrial protein. All Friedreich ataxia patients carry a GAA⋅TTC repeat expansion in the first intron frataxin gene, either homozygous state or compound heterozygosity with other loss-of-function mutations. The GAA inhibits expression through heterochromatin-mediated repression mechanism. Histone modifications that are characteristic...
To obtain quantitative data on the progression of most common spinocerebellar ataxias (SCAs) and identify factors that influence their progression, we initiated EUROSCA natural history study, a multicentric longitudinal cohort study 526 patients with SCA1, SCA2, SCA3, or SCA6. We report results 1- 2-year follow-up visits.As primary outcome measure used Scale for Assessment Rating Ataxia (SARA, 0-40), as secondary Inventory Non-Ataxia Symptoms (INAS, 0-16) count.The annual increase SARA score...
Paroxysmal non-kinesigenic dyskinesia (PNKD) is characterized by spontaneous hyperkinetic attacks that are precipitated alcohol, coffee, stress and fatigue. We report mutations in the myofibrillogenesis regulator 1 (MR-1) gene causing PNKD 50 individuals from eight families. The cause changes (Ala to Val) N-terminal region of two MR-1 isoforms. MR-1L isoform specifically expressed brain localized cell membrane while MR-1S ubiquitously shows diffuse cytoplasmic nuclear localization....