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Article ; Online: AAV2/9-mediated silencing of PMP22 prevents the development of pathological features in a rat model of Charcot-Marie-Tooth disease 1 A.

Gautier, Benoit / Hajjar, Helene / Soares, Sylvia / Berthelot, Jade / Deck, Marie / Abbou, Scarlette / Campbell, Graham / Ceprian, Maria / Gonzalez, Sergio / Fovet, Claire-Maëlle / Schütza, Vlad / Jouvenel, Antoine / Rivat, Cyril / Zerah, Michel / François, Virginie / Le Guiner, Caroline / Aubourg, Patrick / Fledrich, Robert / Tricaud, Nicolas

Nature communications

2021 Volume 12, Issue 1, Page(s) 2356

Abstract: Charcot-Marie-Tooth disease 1 A (CMT1A) results from a duplication of the PMP22 gene ... shRNAs targeting Pmp22 mRNA in animal models of Charcot-Marie-Tooth disease 1 A. Intra-nerve delivery ...

Abstract	Charcot-Marie-Tooth disease 1 A (CMT1A) results from a duplication of the PMP22 gene in Schwann cells and a deficit of myelination in peripheral nerves. Patients with CMT1A have reduced nerve conduction velocity, muscle wasting, hand and foot deformations and foot drop walking. Here, we evaluate the safety and efficacy of recombinant adeno-associated viral vector serotype 9 (AAV2/9) expressing GFP and shRNAs targeting Pmp22 mRNA in animal models of Charcot-Marie-Tooth disease 1 A. Intra-nerve delivery of AAV2/9 in the sciatic nerve allowed widespread transgene expression in resident myelinating Schwann cells in mice, rats and non-human primates. A bilateral treatment restore expression levels of PMP22 comparable to wild-type conditions, resulting in increased myelination and prevention of motor and sensory impairments over a twelve-months period in a rat model of CMT1A. We observed limited off-target transduction and immune response using the intra-nerve delivery route. A combination of previously characterized human skin biomarkers is able to discriminate between treated and untreated animals, indicating their potential use as part of outcome measures.
MeSH term(s)	Animals ; Charcot-Marie-Tooth Disease/genetics ; Charcot-Marie-Tooth Disease/pathology ; Charcot-Marie-Tooth Disease/therapy ; Dependovirus/genetics ; Disease Models, Animal ; Female ; Gene Silencing ; Genetic Therapy/methods ; Genetic Vectors ; Humans ; Macaca fascicularis ; Male ; Mice ; Mice, Inbred C57BL ; Myelin Proteins/antagonists & inhibitors ; Myelin Proteins/genetics ; RNA, Small Interfering/genetics ; Rats ; Rats, Mutant Strains ; Schwann Cells/metabolism ; Schwann Cells/pathology ; Sciatic Nerve/metabolism ; Sciatic Nerve/pathology
Chemical Substances	Myelin Proteins ; PMP22 protein, human ; Pmp22 protein, mouse ; Pmp22 protein, rat ; RNA, Small Interfering
Language	English
Publishing date	2021-04-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-22593-3
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Article ; Online: AAV2/9-mediated silencing of PMP22 prevents the development of pathological features in a rat model of Charcot-Marie-Tooth disease 1 A

Benoit Gautier / Helene Hajjar / Sylvia Soares / Jade Berthelot / Marie Deck / Scarlette Abbou / Graham Campbell / Maria Ceprian / Sergio Gonzalez / Claire-Maëlle Fovet / Vlad Schütza / Antoine Jouvenel / Cyril Rivat / Michel Zerah / Virginie François / Caroline Le Guiner / Patrick Aubourg / Robert Fledrich / Nicolas Tricaud

Nature Communications, Vol 12, Iss 1, Pp 1-

2021 Volume 15

Abstract: Charcot-Marie-Tooth disease 1 A (CMT1A) results from PMP22 gene duplication and is characterized ...

Abstract	Charcot-Marie-Tooth disease 1 A (CMT1A) results from PMP22 gene duplication and is characterized by peripheral nerve myelination deficits. Here, the authors prevent the development of pathological features in a rat model of CMT1A through the local delivery of AAV2/9 expressing shRNAs against PMP22.
Keywords	Science ; Q
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
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Article ; Online: INF2 mutations in Charcot-Marie-Tooth disease with glomerulopathy.

Boyer, Olivia / Nevo, Fabien / Plaisier, Emmanuelle / Funalot, Benoit / Gribouval, Olivier / Benoit, Geneviève / Huynh Cong, Evelyne / Arrondel, Christelle / Tête, Marie-Josèphe / Montjean, Rodrick / Richard, Laurence / Karras, Alexandre / Pouteil-Noble, Claire / Balafrej, Leila / Bonnardeaux, Alain / Canaud, Guillaume / Charasse, Christophe / Dantal, Jacques / Deschenes, Georges /

Deteix, Patrice / Dubourg, Odile / Petiot, Philippe / Pouthier, Dominique / Leguern, Eric / Guiochon-Mantel, Anne / Broutin, Isabelle / Gubler, Marie-Claire / Saunier, Sophie / Ronco, Pierre / Vallat, Jean-Michel / Alonso, Miguel Angel / Antignac, Corinne / Mollet, Géraldine

The New England journal of medicine

2011 Volume 365, Issue 25, Page(s) 2377–2388

Abstract: Background: Charcot-Marie-Tooth neuropathy has been reported to be associated with renal diseases ... We therefore hypothesized that INF2 may be responsible for cases of Charcot-Marie-Tooth neuropathy associated with FSGS ... Methods: We performed direct genotyping of INF2 in 16 index patients with Charcot-Marie-Tooth neuropathy ...

Abstract	Background: Charcot-Marie-Tooth neuropathy has been reported to be associated with renal diseases, mostly focal segmental glomerulosclerosis (FSGS). However, the common mechanisms underlying the neuropathy and FSGS remain unknown. Mutations in INF2 were recently identified in patients with autosomal dominant FSGS. INF2 encodes a formin protein that interacts with the Rho-GTPase CDC42 and myelin and lymphocyte protein (MAL) that are implicated in essential steps of myelination and myelin maintenance. We therefore hypothesized that INF2 may be responsible for cases of Charcot-Marie-Tooth neuropathy associated with FSGS. Methods: We performed direct genotyping of INF2 in 16 index patients with Charcot-Marie-Tooth neuropathy and FSGS who did not have a mutation in PMP22 or MPZ, encoding peripheral myelin protein 22 and myelin protein zero, respectively. Histologic and functional studies were also conducted. Results: We identified nine new heterozygous mutations in 12 of the 16 index patients (75%), all located in exons 2 and 3, encoding the diaphanous-inhibitory domain of INF2. Patients presented with an intermediate form of Charcot-Marie-Tooth neuropathy as well as a glomerulopathy with FSGS on kidney biopsy. Immunohistochemical analysis revealed strong INF2 expression in Schwann-cell cytoplasm and podocytes. Moreover, we demonstrated that INF2 colocalizes and interacts with MAL in Schwann cells. The INF2 mutants perturbed the INF2-MAL-CDC42 pathway, resulting in cytoskeleton disorganization, enhanced INF2 binding to CDC42 and mislocalization of INF2, MAL, and CDC42. Conclusions: INF2 mutations appear to cause many cases of FSGS-associated Charcot-Marie-Tooth neuropathy, showing that INF2 is involved in a disease affecting both the kidney glomerulus and the peripheral nervous system. These findings provide new insights into the pathophysiological mechanisms linking formin proteins to podocyte and Schwann-cell function. (Funded by the Agence Nationale de la Recherche and others.).
MeSH term(s)	Actins/metabolism ; Adolescent ; Adult ; Age of Onset ; Animals ; Charcot-Marie-Tooth Disease/complications ; Charcot-Marie-Tooth Disease/genetics ; Child ; Female ; Glomerulosclerosis, Focal Segmental/etiology ; Heterozygote ; Humans ; Kidney/metabolism ; Male ; Membrane Transport Proteins/metabolism ; Mice ; Microfilament Proteins/genetics ; Microfilament Proteins/metabolism ; Middle Aged ; Mutation ; Myelin Proteins/metabolism ; Myelin and Lymphocyte-Associated Proteolipid Proteins ; Phenotype ; Proteolipids/metabolism ; Schwann Cells/metabolism ; Young Adult
Chemical Substances	Actins ; INF2 protein, human ; MAL protein, human ; Mal protein, mouse ; Membrane Transport Proteins ; Microfilament Proteins ; Myelin Proteins ; Myelin and Lymphocyte-Associated Proteolipid Proteins ; Proteolipids
Language	English
Publishing date	2011-12-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMoa1109122
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Article: Optimized Protocol to Generate Spinal Motor Neuron Cells from Induced Pluripotent Stem Cells from Charcot Marie Tooth Patients.

Faye, Pierre-Antoine / Vedrenne, Nicolas / Miressi, Federica / Rassat, Marion / Romanenko, Sergii / Richard, Laurence / Bourthoumieu, Sylvie / Funalot, Benoît / Sturtz, Franck / Favreau, Frederic / Lia, Anne-Sophie

Brain sciences

2020 Volume 10, Issue 7

Abstract: ... cells from patients. For hereditary peripheral neuropathies, such as Charcot-Marie-Tooth disease (CMT ...

Abstract	Modelling rare neurogenetic diseases to develop new therapeutic strategies is highly challenging. The use of human-induced pluripotent stem cells (hiPSCs) is a powerful approach to obtain specialized cells from patients. For hereditary peripheral neuropathies, such as Charcot-Marie-Tooth disease (CMT) Type II, spinal motor neurons (MNs) are impaired but are very difficult to study. Although several protocols are available to differentiate hiPSCs into neurons, their efficiency is still poor for CMT patients. Thus, our goal was to develop a robust, easy, and reproducible protocol to obtain MNs from CMT patient hiPSCs. The presented protocol generates MNs within 20 days, with a success rate of 80%, using specifically chosen molecules, such as Sonic Hedgehog or retinoic acid. The timing and concentrations of the factors used to induce differentiation are crucial and are given hereby. We then assessed the MNs by optic microscopy, immunocytochemistry (Islet1/2, HB9, Tuj1, and PGP9.5), and electrophysiological recordings. This method of generating MNs from CMT patients in vitro shows promise for the further development of assays to understand the pathological mechanisms of CMT and for drug screening.
Language	English
Publishing date	2020-06-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2651993-8
ISSN	2076-3425
ISSN	2076-3425
DOI	10.3390/brainsci10070407
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Article ; Online: The various Charcot-Marie-Tooth diseases.

Vallat, Jean-Michel / Mathis, Stéphane / Funalot, Benoît

Current opinion in neurology

2013 Volume 26, Issue 5, Page(s) 473–480

Abstract: ... the underlying pathophysiological mechanisms of Charcot-Marie-Tooth (CMT) disease. We also discuss the emerging ...

Abstract	Purpose of review: This review focuses on recent advances in the diagnostic approaches and the underlying pathophysiological mechanisms of Charcot-Marie-Tooth (CMT) disease. We also discuss the emerging therapies for this hereditary neuropathy. Recent findings: To date, numerous genes are implicated in CMT, and new genes have recently been found to be associated with this neuropathy (INF2, FBLN5, etc.). Some specific or evocative clinical signs of CMT subtypes (proteinuria with INF2 mutations, etc.) have been identified. Characteristic pathological findings, which may suggest gene mutations, are also recognized by nerve biopsy (mainly ultrastructural lesions). Summary: CMT disease is the most common inherited neuromuscular disorder, with a fairly homogeneous clinical phenotype (progressive distal muscle weakness and atrophy, foot deformities, distal sensory loss, and depressed tendon reflexes). With more than 40 genes implicated, an update of the present and rather confusing classification of CMT is needed. Over the last few years, new mutated genes have been discovered. Although nerve biopsy is not routinely carried out in CMT neuropathies, it may show characteristic features, which can orientate the search for the mutated gene. There are currently no effective medications for CMT, but clinical trials are ongoing or planned.
MeSH term(s)	Animals ; Charcot-Marie-Tooth Disease/classification ; Charcot-Marie-Tooth Disease/diagnosis ; Charcot-Marie-Tooth Disease/genetics ; Charcot-Marie-Tooth Disease/therapy ; Genetic Predisposition to Disease/genetics ; Genetic Testing ; Humans ; Mutation/genetics ; Pathology, Molecular/methods ; Phenotype
Language	English
Publishing date	2013-10
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1182686-1
ISSN	1473-6551 ; 1350-7540
ISSN (online)	1473-6551
ISSN	1350-7540
DOI	10.1097/WCO.0b013e328364c04b
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Article: La maladie de Charcot-Marie-Tooth.

Vallat, Jean-Michel / Funalot, Benoît

Medecine sciences : M/S

2010 Volume 26, Issue 10, Page(s) 842–847

Abstract: Charcot-Marie-Tooth (CMT) <> is the generic name given to a group of genetic disorders ...

Title translation	Charcot-Marie-Tooth (CMT) disease: an update.
Abstract	Charcot-Marie-Tooth (CMT) <<disease>> is the generic name given to a group of genetic disorders characterized by a relatively isolated dysfunction of peripheral nerves, with combined motor and sensory impairment. These CMT syndromes are the most frequent genetically-determined peripheral neuropathies, with a global prevalence between 4.7 and 36/100,000. Their clinical phenotype is predominantly motor, with a grossly symmetrical distal amyotrophy involving both lower and upper limbs. Mode of inheritance is variable: autosomal dominant, autosomal recessive or X-linked. Apparently sporadic forms can be a difficult diagnosis and they must be considered in all patients with a chronic polyneuropathy which is not clearly of acquired origin. During the last two decades, the identification of more than 25 genes mutated in CMT syndromes has complicated the classification of these disorders. Knowledge of the function of some of these genes has improved our understanding of the pathogenesis of myelinic or axonal dysfunction in CMT, but for some others their function remains elusive or unknown.
MeSH term(s)	Charcot-Marie-Tooth Disease/epidemiology ; Charcot-Marie-Tooth Disease/genetics ; Charcot-Marie-Tooth Disease/pathology ; Chromosome Mapping ; Genes, Dominant ; Genes, Recessive ; Hereditary Sensory and Motor Neuropathy/genetics ; Humans ; Peripheral Nerves/pathology ; Phenotype ; Prevalence ; Syndrome
Language	French
Publishing date	2010-10
Publishing country	France
Document type	English Abstract ; Journal Article ; Review
ZDB-ID	632733-3
ISSN	1958-5381 ; 0767-0974
ISSN (online)	1958-5381
ISSN	0767-0974
DOI	10.1051/medsci/20102610842
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Article ; Online: Peripheral myelin protein 22 gene duplication with atypical presentations: a new example of the wide spectrum of Charcot-Marie-Tooth 1A disease.

Mathis, Stéphane / Corcia, Philippe / Tazir, Meriem / Camu, William / Magdelaine, Corinne / Latour, Philippe / Biberon, Julien / Guennoc, Anne-Marie / Richard, Laurence / Magy, Laurent / Funalot, Benoît / Vallat, Jean-Michel

Neuromuscular disorders : NMD

2014 Volume 24, Issue 6, Page(s) 524–528

Abstract: Charcot-Marie-Tooth type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies ... in Charcot-Marie-Tooth diseases. ...

Abstract	Charcot-Marie-Tooth type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are both autosomal-dominant disorders linked to peripheral myelin anomalies. CMT1A is associated with a Peripheral Myelin Protein 22 (PMP22) duplication, whereas HNPP is due to a PMP22 deletion on chromosome 17. In spite of this crucial difference, we report three observations of patients with the 1.4 megabase CMT1A duplication and atypical presentation (electrophysiological, clinical or pathological): a 10 year-old girl with tomaculous lesions on nerve biopsy; a 26 year-old woman with recurrent paresthesiae and block conduction on the electrophysiological study; a 46 year-old woman with transient recurrent nerve palsies mimicking HNPP. These observations highlight the wide spectrum of CMT1A and the overlap between CMT1A and HNPP (both linked to the PMP22 gene), and finally illustrate the complexity of the genotype-phenotype correlations in Charcot-Marie-Tooth diseases.
MeSH term(s)	Adult ; Charcot-Marie-Tooth Disease/diagnosis ; Charcot-Marie-Tooth Disease/genetics ; Child ; Female ; Gene Duplication ; Humans ; Middle Aged ; Myelin Proteins/genetics ; Pedigree
Chemical Substances	Myelin Proteins ; PMP22 protein, human
Language	English
Publishing date	2014-06
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	1077681-3
ISSN	1873-2364 ; 0960-8966
ISSN (online)	1873-2364
ISSN	0960-8966
DOI	10.1016/j.nmd.2014.03.014
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Article ; Online: Erratum to: An exploratory randomised double-blind and placebo-controlled phase 2 study of a combination of baclofen, naltrexone and sorbitol (PXT3003) in patients with Charcot-Marie-Tooth disease type 1A.

Attarian, Shahram / Vallat, Jean-Michel / Magy, Laurent / Funalot, Benoît / Gonnaud, Pierre-Marie / Lacour, Arnaud / Péréon, Yann / Dubourg, Odile / Pouget, Jean / Micallef, Joëlle / Franques, Jérôme / Lefebvre, Marie-Noëlle / Ghorab, Karima / Al-Moussawi, Mahmoud / Tiffreau, Vincent / Preudhomme, Marguerite / Magot, Armelle / Leclair-Visonneau, Laurène / Stojkovic, Tanya /

Bossi, Laura / Lehert, Philippe / Gilbert, Walter / Bertrand, Viviane / Mandel, Jonas / Milet, Aude / Hajj, Rodolphe / Boudiaf, Lamia / Scart-Grès, Catherine / Nabirotchkin, Serguei / Guedj, Mickael / Chumakov, Ilya / Cohen, Daniel

Orphanet journal of rare diseases

2016 Volume 11, Issue 1, Page(s) 92

Language	English
Publishing date	2016-07-07
Publishing country	England
Document type	Published Erratum
ISSN	1750-1172
ISSN (online)	1750-1172
DOI	10.1186/s13023-016-0463-6
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Article ; Online: An exploratory randomised double-blind and placebo-controlled phase 2 study of a combination of baclofen, naltrexone and sorbitol (PXT3003) in patients with Charcot-Marie-Tooth disease type 1A.

Orphanet journal of rare diseases

2014 Volume 9, Page(s) 199

Abstract: Background: Charcot-Marie-Tooth type 1A disease (CMT1A) is a rare orphan inherited neuropathy ... events. Efficacy was assessed using the Charcot-Marie-Tooth Neuropathy Score (CMTNS) and the Overall ...

Abstract	Background: Charcot-Marie-Tooth type 1A disease (CMT1A) is a rare orphan inherited neuropathy caused by an autosomal dominant duplication of a gene encoding for the structural myelin protein PMP22, which induces abnormal Schwann cell differentiation and dysmyelination, eventually leading to axonal suffering then loss and muscle wasting. We favour the idea that diseases can be more efficiently treated when targeting multiple disease-relevant pathways. In CMT1A patients, we therefore tested the potential of PXT3003, a low-dose combination of three already approved compounds (baclofen, naltrexone and sorbitol). Our study conceptually builds on preclinical experiments highlighting a pleiotropic mechanism of action that includes downregulation of PMP22. The primary objective was to assess safety and tolerability of PXT3003. The secondary objective aimed at an exploratory analysis of efficacy of PXT3003 in CMT1A, to be used for designing next clinical development stages (Phase 2b/3). Methods: 80 adult patients with mild-to-moderate CMT1A received in double-blind for 1 year Placebo or one of the three increasing doses of PXT3003 tested, in four equal groups. Safety and tolerability were assessed with the incidence of related adverse events. Efficacy was assessed using the Charcot-Marie-Tooth Neuropathy Score (CMTNS) and the Overall Neuropathy Limitations Scale (ONLS) as main endpoints, as well as various clinical and electrophysiological outcomes. Results: This trial confirmed the safety and tolerability of PXT3003. The highest dose (HD) showed consistent evidence of improvement beyond stabilization. CMTNS and ONLS, with a significant improvement of respectively of 8% (0.4% - 16.2%) and 12.1% (2% - 23.2%) in the HD group versus the pool of all other groups, appear to be the most sensitive clinical endpoints to treatment despite their quasi-stability over one year under Placebo. Patients who did not deteriorate over one year were significantly more frequent in the HD group. Conclusions: These results confirm that PXT3003 deserves further investigation in adults and could greatly benefit CMT1A-diagnosed children, usually less affected than adults. Trial registration: EudraCT Number: 2010-023097-40. ClinicalTrials.gov Identifier: NCT01401257. The Committee for Orphan Medicinal Products issued in February 2014 a positive opinion on the application for orphan designation for PXT3003 (EMA/OD/193/13).
MeSH term(s)	Adult ; Baclofen/administration & dosage ; Charcot-Marie-Tooth Disease/diagnosis ; Charcot-Marie-Tooth Disease/drug therapy ; Double-Blind Method ; Drug Therapy, Combination ; Female ; Humans ; Male ; Middle Aged ; Naltrexone/administration & dosage ; Sorbitol/administration & dosage
Chemical Substances	Sorbitol (506T60A25R) ; Naltrexone (5S6W795CQM) ; Baclofen (H789N3FKE8)
Language	English
Publishing date	2014-12-18
Publishing country	England
Document type	Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ISSN	1750-1172
ISSN (online)	1750-1172
DOI	10.1186/s13023-014-0199-0
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Article ; Online: Genotype-phenotype correlations in Charcot-Marie-Tooth disease type 2 caused by mitofusin 2 mutations.

Calvo, Judith / Funalot, Benoît / Ouvrier, Robert A / Lazaro, Leila / Toutain, Annick / De Mas, Philippe / Bouche, Pierre / Gilbert-Dussardier, Brigitte / Arne-Bes, Marie-Christine / Carrière, Jean-Pierre / Journel, Hubert / Minot-Myhie, Marie-Christine / Guillou, Claire / Ghorab, Karima / Magy, Laurent / Sturtz, Franck / Vallat, Jean-Michel / Magdelaine, Corinne

Archives of neurology

2009 Volume 66, Issue 12, Page(s) 1511–1516

Abstract: Background: Mutations in the gene encoding mitofusin 2 (MFN2) cause Charcot-Marie ...

Abstract	Background: Mutations in the gene encoding mitofusin 2 (MFN2) cause Charcot-Marie-Tooth disease type 2 (CMT2), with heterogeneity concerning severity and associated clinical features. Objective: To describe MFN2 mutations and associated phenotypes in patients with hereditary motor and sensory neuropathy (HMSN). Design: Direct sequencing of the MFN2 gene and clinical investigations of patients with MFN2 mutations. Setting: Molecular genetics laboratory of a university hospital and the Limoges National Referral Center for Rare Peripheral Neuropathies. Patients: One hundred fifty index patients with HMSN and a median motor nerve conduction velocity of 25 m/s or greater and without mutations in the genes encoding connexin 32 and myelin protein zero. Main outcome measures: Results of genetic analyses and phenotypic observations. Results: Twenty different missense mutations were identified in 20 index patients. Mutation frequency was 19 of 107 (17.8%) in patients with CMT2 and 1 of 43 (2.3%) in patients with a median motor nerve conduction velocity less than 38 m/s. Four patients had proven de novo mutations, 8 families had autosomal dominant inheritance, and 3 had autosomal recessive inheritance. The remaining 5 patients were sporadic cases with heterozygous mutations. Phenotypes varied from mild forms to early-onset severe forms. Additional features were encountered in 8 patients (32%). Six patients underwent sural nerve biopsy: electronic microscopy showed prominent mitochondrial abnormalities on longitudinal sections. Conclusions: MFN2 mutations are a frequent cause of CMT2, with variable severity and either dominant or recessive inheritance. MFN2 gene testing must be a first-line analysis in axonal HMSN irrespective of the mode of inheritance or the severity of the peripheral neuropathy.
MeSH term(s)	Adolescent ; Adult ; Aged ; Charcot-Marie-Tooth Disease/classification ; Charcot-Marie-Tooth Disease/genetics ; Charcot-Marie-Tooth Disease/pathology ; Child ; Child, Preschool ; Female ; GTP Phosphohydrolases ; Genes, Dominant ; Genes, Recessive ; Genetic Markers/genetics ; Genotype ; Humans ; Male ; Membrane Proteins/genetics ; Middle Aged ; Mitochondrial Proteins/genetics ; Mutation, Missense/genetics ; Phenotype ; Severity of Illness Index ; Young Adult
Chemical Substances	Genetic Markers ; Membrane Proteins ; Mitochondrial Proteins ; GTP Phosphohydrolases (EC 3.6.1.-) ; MFN2 protein, human (EC 3.6.1.-)
Language	English
Publishing date	2009-12
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80049-1
ISSN	1538-3687 ; 0003-9942
ISSN (online)	1538-3687
ISSN	0003-9942
DOI	10.1001/archneurol.2009.284
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