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المؤلفون: Sabrina Sacconi, Leonardo Salviati, Claude Desnuelle
المساهمون: Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
المصدر: BBA-Biochimica et Biophysica Acta
BBA-Biochimica et Biophysica Acta, Elsevier, 2015, 1852 (4), pp.607-614مصطلحات موضوعية: DUX4, Chromosomal Proteins, Non-Histone, Apoptosis, Repetitive Sequences, Muscular Dystrophies, Epigenesis, Genetic, 0302 clinical medicine, Facioscapulohumeral muscular dystrophy, [SDV.BDD]Life Sciences [q-bio]/Development Biology, ComputingMilieux_MISCELLANEOUS, Genetics, 0303 health sciences, DNA methylation, Subtelomere, Chromatin, 3. Good health, Chromosomal Proteins, Pair 4, Genetic Diseases, Molecular Medicine, Epigenetics, Chromosomes, Human, Pair 4, Human, musculoskeletal diseases, congenital, hereditary, and neonatal diseases and abnormalities, Locus (genetics), Biology, Chromosomes, 03 medical and health sciences, Prophase, Genetic, Subtelomeric repeat, medicine, Animals, Humans, Allele, Molecular Biology, Alleles, 030304 developmental biology, Repetitive Sequences, Nucleic Acid, Homeodomain Proteins, Nucleic Acid, SMCHD1, Genetic Diseases, Inborn, Non-Histone, medicine.disease, Chromatin Assembly and Disassembly, Inborn, Genetic Loci, Mutation, 030217 neurology & neurosurgery, Epigenesis
الوصف: Facioscapulohumeral muscular dystrophy (FSHD) is characterized by a typical and asymmetric pattern of muscle involvement and disease progression. Two forms of FSHD, FSHD1 and FSHD2, have been identified displaying identical clinical phenotype but different genetic and epigenetic basis. Autosomal dominant FSHD1 (95% of patients) is characterized by chromatin relaxation induced by pathogenic contraction of a macrosatellite repeat called D4Z4 located on the 4q subtelomere (FSHD1 patients harbor 1 to 10 D4Z4 repeated units). Chromatin relaxation is associated with inappropriate expression of DUX4, a retrogene, which in muscles induces apoptosis and inflammation. Consistent with this hypothesis, individuals carrying zero repeat on chromosome 4 do not develop FSHD1. Not all D4Z4 contracted alleles cause FSHD. Distal to the last D4Z4 unit, a polymorphic site with two allelic variants has been identified: 4qA and 4qB. 4qA is in cis with a functional polyadenylation consensus site. Only contractions on 4qA alleles are pathogenic because the DUX4 transcript is polyadenylated and translated into stable protein. FSHD2 is instead a digenic disease. Chromatin relaxation of the D4Z4 locus is caused by heterozygous mutations in the SMCHD1 gene encoding a protein essential for chromatin condensation. These patients also harbor at least one 4qA allele in order to express stable DUX4 transcripts. FSHD1 and FSHD2 may have an additive effect: patients harboring D4Z4 contraction and SMCHD1 mutations display a more severe clinical phenotype than with either defect alone. Knowledge of the complex genetic and epigenetic defects causing these diseases is essential in view of designing novel therapeutic strategies. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::732b8f65d06151b4f77d8617ca84e446Test
https://pubmed.ncbi.nlm.nih.gov/24882751Test -
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المؤلفون: Douglass M. Turnbull, A. Saunières, B. Mousson de Camaret, Véronique Paquis-Flucklinger, B. Vialettes, Claude Desnuelle, H. Narbonne, D. Perucca-Lostanlen, Robert W. Taylor, C Hayes
المصدر: Biochimica et biophysica acta. 1588(3)
مصطلحات موضوعية: Mitochondrial DNA, Genotype, Mutant, Respiratory chain, Biology, Mitochondrion, Deafness, DNA, Mitochondrial, Cell Fusion, Diabetes Complications, 03 medical and health sciences, Diabetes mellitus genetics, Electron Transport Complex III, 0302 clinical medicine, Multienzyme Complexes, Diabetes Mellitus, Humans, Point Mutation, NADH, NADPH Oxidoreductases, Mitochondrial diabetes, Molecular Biology, Transmitochondrial cybrid, 030304 developmental biology, Genetics, 0303 health sciences, Homoplasmy, Electron Transport Complex I, Base Sequence, Point mutation, Electron Transport Complex II, Fibroblasts, Blotting, Northern, Molecular biology, Heteroplasmy, RNA, Transfer, Glu, Clone Cells, Succinate Dehydrogenase, Molecular Medicine, Oxidoreductases, 030217 neurology & neurosurgery
الوصف: A heteroplasmic T to C transition at nucleotide position 14709 in the mitochondrial tRNA glutamic acid (tRNA(Glu)) gene has previously been associated with maternally inherited diabetes and deafness (MIDD). To investigate the pathogenic mechanism of the T14709C mutation, we have constructed transmitochondrial cell lines by transferring fibroblasts mitochondria from a patient with the mutation into human cells lacking mitochondrial DNA (mtDNA) (rho degrees cells). Clonal cybrid cell lines were obtained containing various levels of the heteroplasmic mutation, or exclusively mutated or wild-type mtDNA. Measurement of respiratory chain enzymatic activities failed to detect a difference between the homoplasmic mutant and homoplasmic wild-type cybrid cell lines. However, a subtle decrease in the steady-state levels of tRNA(Glu) transcripts in some mutant clones. Our studies suggest that the T14709C mutation is insufficient to lead impairment of mitochondrial function in homoplasmic osteosarcoma cybrid clones, and that we cannot exclude that the T14709C mutation affects mitochondrial function by a yet unidentified mechanism.
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::93d57488e5e143ad1c6b4ea6a8969579Test
https://pubmed.ncbi.nlm.nih.gov/12393175Test