charcot marie tooth disease

Summary

Summary: A hereditary motor and sensory neuropathy transmitted most often as an autosomal dominant trait and characterized by progressive distal wasting and loss of reflexes in the muscles of the legs (and occasionally involving the arms). Onset is usually in the second to fourth decade of life. This condition has been divided into two subtypes, hereditary motor and sensory neuropathy (HMSN) types I and II. HMSN I is associated with abnormal nerve conduction velocities and nerve hypertrophy, features not seen in HMSN II. (Adams et al., Principles of Neurology, 6th ed, p1343)

Top Publications

  1. ncbi Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A
    Stephan Zuchner
    Department of Neuropathology, University Hospital, RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany
    Nat Genet 36:449-51. 2004
  2. pmc Mutations in the small GTP-ase late endosomal protein RAB7 cause Charcot-Marie-Tooth type 2B neuropathy
    Kristien Verhoeven
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, Born Bunge Foundation, University of Antwerp, Antwerp, Belgium
    Am J Hum Genet 72:722-7. 2003
  3. pmc Mutation of FIG4 causes neurodegeneration in the pale tremor mouse and patients with CMT4J
    Clement Y Chow
    Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA
    Nature 448:68-72. 2007
  4. ncbi Charcot-Marie-Tooth disease due to a de novo mutation of the RAB7 gene
    F Meggouh
    Neurogenetics Department, AMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
    Neurology 67:1476-8. 2006
  5. ncbi Reliability and validity of the CMT neuropathy score as a measure of disability
    M E Shy
    Department of Neurology, Wayne State University, Detroit, MI 48201, USA
    Neurology 64:1209-14. 2005
  6. ncbi Ganglioside-induced differentiation-associated protein-1 is mutant in Charcot-Marie-Tooth disease type 4A/8q21
    Rachel V Baxter
    Center for Human Genetics, Institute of Genomic Sciences and Policy, Research Park Building II Room 105, Box 2903, Duke University Medical Center, Durham, North Carolina 27710, USA
    Nat Genet 30:21-2. 2002
  7. ncbi Loss of Mtmr2 phosphatase in Schwann cells but not in motor neurons causes Charcot-Marie-Tooth type 4B1 neuropathy with myelin outfoldings
    Annalisa Bolis
    Dulbecco Telethon Institute, San Raffaele Scientific Institute, 20132 Milan, Italy
    J Neurosci 25:8567-77. 2005
  8. pmc Mutations in a gene encoding a novel SH3/TPR domain protein cause autosomal recessive Charcot-Marie-Tooth type 4C neuropathy
    Jan Senderek
    Department of Human Genetics, Aachen University of Technology, Aachen, Germany
    Am J Hum Genet 73:1106-19. 2003
  9. ncbi A mutation in periaxin is responsible for CMT4F, an autosomal recessive form of Charcot-Marie-Tooth disease
    A Guilbot
    INSERM U289, Hopital de la Salpetriere, 47 Boulevard de l Hopital, Paris, France
    Hum Mol Genet 10:415-21. 2001
  10. pmc Ganglioside-induced differentiation associated protein 1 is a regulator of the mitochondrial network: new implications for Charcot-Marie-Tooth disease
    Axel Niemann
    Institute of Cell Biology, Department of Biology, Swiss Federal Institute of Technology, ETH Honggerberg, 8093 Zurich, Switzerland
    J Cell Biol 170:1067-78. 2005

Detail Information

Publications266 found, 100 shown here

  1. ncbi Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A
    Stephan Zuchner
    Department of Neuropathology, University Hospital, RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany
    Nat Genet 36:449-51. 2004
  2. pmc Mutations in the small GTP-ase late endosomal protein RAB7 cause Charcot-Marie-Tooth type 2B neuropathy
    Kristien Verhoeven
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, Born Bunge Foundation, University of Antwerp, Antwerp, Belgium
    Am J Hum Genet 72:722-7. 2003
    ..The alignment of RAB7 orthologs shows that both missense mutations target highly conserved amino acid residues. RAB7 is ubiquitously expressed, and we found expression in sensory and motor neurons...
  3. pmc Mutation of FIG4 causes neurodegeneration in the pale tremor mouse and patients with CMT4J
    Clement Y Chow
    Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA
    Nature 448:68-72. 2007
    ..This novel form of autosomal recessive Charcot-Marie-Tooth disorder is designated CMT4J...
  4. ncbi Charcot-Marie-Tooth disease due to a de novo mutation of the RAB7 gene
    F Meggouh
    Neurogenetics Department, AMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
    Neurology 67:1476-8. 2006
    ..471G>C, p.Lys157Asn missense mutation. This observation strongly supports the hypothesis that RAB7 mutations are responsible for CMT2B...
  5. ncbi Reliability and validity of the CMT neuropathy score as a measure of disability
    M E Shy
    Department of Neurology, Wayne State University, Detroit, MI 48201, USA
    Neurology 64:1209-14. 2005
    ..To determine the validity and reliability of the Charcot-Marie-Tooth disease (CMT) neuropathy score (CMTNS) in patients with inherited neuropathy...
  6. ncbi Ganglioside-induced differentiation-associated protein-1 is mutant in Charcot-Marie-Tooth disease type 4A/8q21
    Rachel V Baxter
    Center for Human Genetics, Institute of Genomic Sciences and Policy, Research Park Building II Room 105, Box 2903, Duke University Medical Center, Durham, North Carolina 27710, USA
    Nat Genet 30:21-2. 2002
    ..We found three different mutations in four different Tunisian families-two nonsense and one missense mutation. How mutations in GDAP1 lead to CMT4A remains to be understood...
  7. ncbi Loss of Mtmr2 phosphatase in Schwann cells but not in motor neurons causes Charcot-Marie-Tooth type 4B1 neuropathy with myelin outfoldings
    Annalisa Bolis
    Dulbecco Telethon Institute, San Raffaele Scientific Institute, 20132 Milan, Italy
    J Neurosci 25:8567-77. 2005
    ..Thus, therapeutical approaches might be designed in the future to specifically deliver the Mtmr2 phospholipid phosphatase to Schwann cells in affected nerves...
  8. pmc Mutations in a gene encoding a novel SH3/TPR domain protein cause autosomal recessive Charcot-Marie-Tooth type 4C neuropathy
    Jan Senderek
    Department of Human Genetics, Aachen University of Technology, Aachen, Germany
    Am J Hum Genet 73:1106-19. 2003
    ..Comparative sequence alignments indicate that members of this protein family contain multiple SH3 and TPR domains that are likely involved in the formation of protein complexes...
  9. ncbi A mutation in periaxin is responsible for CMT4F, an autosomal recessive form of Charcot-Marie-Tooth disease
    A Guilbot
    INSERM U289, Hopital de la Salpetriere, 47 Boulevard de l Hopital, Paris, France
    Hum Mol Genet 10:415-21. 2001
    ..These data confirm the importance of the periaxin proteins to normal Schwann cell function and substantiate the utility of the periaxin-null mouse as a model of ARCMT disease...
  10. pmc Ganglioside-induced differentiation associated protein 1 is a regulator of the mitochondrial network: new implications for Charcot-Marie-Tooth disease
    Axel Niemann
    Institute of Cell Biology, Department of Biology, Swiss Federal Institute of Technology, ETH Honggerberg, 8093 Zurich, Switzerland
    J Cell Biol 170:1067-78. 2005
    ..Our data indicate that an exquisitely tight control of mitochondrial dynamics, regulated by GDAP1, is crucial for the proper function of myelinated peripheral nerves...
  11. ncbi Mutation of a putative protein degradation gene LITAF/SIMPLE in Charcot-Marie-Tooth disease 1C
    V A Street
    V M Bloedel Hearing Research Center, Department of Otolaryngology HNS, University of Washington, Seattle 98195, USA
    Neurology 60:22-6. 2003
    ..Charcot-Marie-Tooth (CMT) neuropathy is a heterogeneous group of inherited disorders of the peripheral nervous system. The authors recently mapped an autosomal dominant demyelinating form of CMT type 1 (CMT1C) to chromosome 16p13.1-p12.3...
  12. ncbi The natural history of Charcot-Marie-Tooth type 1A in adults: a 5-year follow-up study
    Camiel Verhamme
    Department of Neurology and Clinical Neurophysiology, H2 222, Academic Medical Centre, University of Amsterdam, PO Box 22660, 1100 DD Amsterdam, The Netherlands
    Brain 132:3252-62. 2009
    ..The slow increase in physical disability in adulthood may well be explained by decreased reserves and compensatory mechanisms together with progression of skeletal deformations due to muscle weakness...
  13. pmc Loss of the inactive myotubularin-related phosphatase Mtmr13 leads to a Charcot-Marie-Tooth 4B2-like peripheral neuropathy in mice
    Fred L Robinson
    Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 105:4916-21. 2008
    ..Mtmr13-deficient mice will be an essential tool for studying how the loss of MTMR13 leads to CMT4B2...
  14. ncbi Schwann cells and the pathogenesis of inherited motor and sensory neuropathies (Charcot-Marie-Tooth disease)
    Philipp Berger
    Institute of Cell Biology, Department of Biology, ETH Zurich, Zurich, Switzerland
    Glia 54:243-57. 2006
    ..These networks include the control of myelin formation and stability, membrane trafficking, intracellular protein sorting and quality control, and may extend to mitochondrial dynamics and basic protein biosynthesis...
  15. ncbi Connexin mutations in X-linked Charcot-Marie-Tooth disease
    J Bergoffen
    Department of Neurology, University of Pennsylvania Medical School, Children s Hospital of Philadelphia 19104
    Science 262:2039-42. 1993
    ..These findings, a demonstration of inherited defects in a gap junction protein, suggest that connexin32 plays an important role in peripheral nerve...
  16. ncbi A novel RAB7 mutation associated with ulcero-mutilating neuropathy
    Henry Houlden
    University Department of Clinical Neurosciences, Royal Free Campus, Royal Free and University College Medical School, University College London, United Kingdom
    Ann Neurol 56:586-90. 2004
    ..The mutation is situated adjacent to a previously identified valine to methionine mutation at codon 162, implying a hotspot for mutations in the highly conserved C terminus of RAB7...
  17. ncbi Disease mechanisms and potential therapeutic strategies in Charcot-Marie-Tooth disease
    P Young
    Department of Biology, Institute of Cell Biology, Swiss Federal Institute of Technology, , 8093, , Switzerland
    Brain Res Brain Res Rev 36:213-21. 2001
    ..Furthermore, we will review how this gain of knowledge about CMT may open new avenues to the development of novel treatment strategies...
  18. ncbi Mutations in the HSP27 (HSPB1) gene cause dominant, recessive, and sporadic distal HMN/CMT type 2
    H Houlden
    Department of Molecular Neurosciences, Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK
    Neurology 71:1660-8. 2008
    ....
  19. ncbi Mutant small heat-shock protein 27 causes axonal Charcot-Marie-Tooth disease and distal hereditary motor neuropathy
    Oleg V Evgrafov
    Department of Psychiatry, New York State Psychiatric Institute Research Foundation for Mental Hygiene, Unit 28, 1051 Riverside Drive, New York, New York 10032, USA
    Nat Genet 36:602-6. 2004
    ..Cotransfection of neurofilament light chain (NEFL) and mutant HSPB1 resulted in altered neurofilament assembly in cells devoid of cytoplasmic intermediate filaments...
  20. ncbi Charcot-Marie-Tooth type 4B is caused by mutations in the gene encoding myotubularin-related protein-2
    A Bolino
    Wellcome Trust Centre for Human Genetics, Oxford, UK
    Nat Genet 25:17-9. 2000
    ..Using a positional-cloning strategy, we identified in unrelated CMT4B patients mutations occurring in the gene MTMR2, encoding myotubularin-related protein-2, a dual specificity phosphatase (DSP)...
  21. ncbi GDAP1, the protein causing Charcot-Marie-Tooth disease type 4A, is expressed in neurons and is associated with mitochondria
    Laia Pedrola
    Laboratory of Genetics and Molecular Medicine, Department of Genomics and Proteomics, Instituto de Biomedicina, CSIC, Valencia, Spain
    Hum Mol Genet 14:1087-94. 2005
    ..We postulate that GDAP1 may be related to the maintenance of the mitochondrial network...
  22. ncbi Neuropathy progression in Charcot-Marie-Tooth disease type 1A
    M E Shy
    Wayne State University, Department of Neurology, Center for Molecular Medicine and Genetics, 421 Ea Canfield, Detroit, MI 48201, USA
    Neurology 70:378-83. 2008
    ..To determine the rate of disease progression in Charcot-Marie-Tooth disease type 1A (CMT1A)...
  23. ncbi Autosomal-recessive forms of demyelinating Charcot-Marie-Tooth disease
    O Dubourg
    INSERM U679 ex U289, La Pitie Salpetriere Hospital, AP HP, Paris, France
    Neuromolecular Med 8:75-86. 2006
    ..In this review, we will focus on the particular clinical and/or neuropathological features of the phenotype caused by mutations in each of these genes, which might guide molecular diagnosis...
  24. ncbi Early onset severe and late-onset mild Charcot-Marie-Tooth disease with mitofusin 2 (MFN2) mutations
    K W Chung
    Department of Neurology and Ewha Medical Research Center, Ewha Woman s University, College of Medicine, Dongdaemun Hospital, 70 Jongno 6 ga, Jongno gu, 110 783, Seoul, Korea E mail
    Brain 129:2103-18. 2006
    ..Phenotypes were significantly different in the early and late disease-onset groups. Our findings suggest that HMSN VI might be a variant of the early onset severe CMT2A phenotype...
  25. pmc Charcot-Marie-Tooth disease
    Kinga Szigeti
    Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA
    Eur J Hum Genet 17:703-10. 2009
    ..Population based studies have determined the contributions of the various genes to disease burden enabling evidence-based approaches to genetic testing...
  26. ncbi Mutational analysis of PMP22, MPZ, GJB1, EGR2 and NEFL in Korean Charcot-Marie-Tooth neuropathy patients
    Byung Ok Choi
    Department of Neurology and Ewha Medical Research Center, Ewha Womans University College of Medicine, Seoul 110 783, Korea
    Hum Mutat 24:185-6. 2004
    ..We described the identified mutations and phenotype-genotype correlations based on nerve conduction studies...
  27. ncbi Ascorbic acid for Charcot-Marie-Tooth disease type 1A in children: a randomised, double-blind, placebo-controlled, safety and efficacy trial
    Joshua Burns
    Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, and Institute for Neuromuscular Research, Children s Hospital at Westmead, Sydney, NSW, Australia
    Lancet Neurol 8:537-44. 2009
    ..We tested the efficacy and safety of ascorbic acid supplementation in children with CMT1A...
  28. ncbi Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease
    Stephan Zuchner
    Center for Human Genetics, Duke University Medical Center, Durham, North Carolina, USA
    Nat Genet 37:289-94. 2005
    ..Additionally, in the Australian and Belgian pedigrees, which carry two different mutations affecting the same amino acid, Lys558, CMT cosegregated with neutropenia, which has not previously been associated with CMT neuropathies...
  29. ncbi The Roussy-Lévy family: from the original description to the gene
    V Plante-Bordeneuve
    Department of Neurology, Centre Hospitalier Universitaire de Bicetre, Universite Paris Sud, Le Kremlin Bicetre, France
    Ann Neurol 46:770-3. 1999
    ..These findings show that the Roussy-Lévy family belongs to the CMT-1B subtype and has original morphological and genetic features...
  30. pmc Six novel connexin32 (GJB1) mutations in X-linked Charcot-Marie-Tooth disease
    M J Lee
    Department of Molecular Pathogenesis, Institute of Neurology, Queen Square, London WC1N 3BG, UK
    J Neurol Neurosurg Psychiatry 73:304-6. 2002
    ..Affected members in these six families had typical signs of CMT but in some affected members of three families there was additional central nervous system involvement or deafness in the absence of any other explanation other than CMT...
  31. ncbi Clinical and electrophysiologic features of CMT2A with mutations in the mitofusin 2 gene
    Victoria H Lawson
    Department of Neurology, University of Utah School of Medicine, Salt Lake City, UT 84132 2305, USA
    Neurology 65:197-204. 2005
    ..The authors report three additional CMT2A families associated with novel mutations in highly conserved regions of the Mfn2 GTPase domain...
  32. ncbi De-novo mutation in hereditary motor and sensory neuropathy type I
    J E Hoogendijk
    Department of Neurology, Academic Medical Center, Amsterdam, The Netherlands
    Lancet 339:1081-2. 1992
    ..This finding has important implications for genetic counselling of isolated patients with HMSN I...
  33. pmc Disruption of Mtmr2 produces CMT4B1-like neuropathy with myelin outfolding and impaired spermatogenesis
    Alessandra Bolino
    Dulbecco Telethon Institute, San Raffaele Scientific Institute, 20132 Milan, Italy
    J Cell Biol 167:711-21. 2004
    ..We propose that Schwann cell-autonomous loss of Mtmr2-Dlg1 interaction dysregulates membrane homeostasis in the paranodal region, thereby producing outfolding and recurrent loops of myelin...
  34. ncbi Medication-induced exacerbation of neuropathy in Charcot Marie Tooth disease
    Louis H Weimer
    Department of Neurology, Columbia University College of Physicians and Surgeons, The Neurological Institute, 710 West 168th Street, Unit 55, New York, NY 10032, USA
    J Neurol Sci 242:47-54. 2006
    ..Drug-induced exacerbation of Charcot Marie Tooth disease (CMT) neuropathy is a common concern; a list of potential drugs to avoid is maintained by the CMT ..
  35. ncbi Focally folded myelin in Charcot-Marie-Tooth neuropathy type 1B with Ser49Leu in the myelin protein zero
    G M Fabrizi
    Department of Neurological and Visual Sciences, University of Verona, Policlinico Giambattista Rossi, Italy
    Acta Neuropathol 100:299-304. 2000
    ....
  36. ncbi Clinical, electrophysiological and molecular genetic characteristics of 93 patients with X-linked Charcot-Marie-Tooth disease
    O Dubourg
    INSERM U289, Hopital de la Salpetriere, Paris, France
    Brain 124:1958-67. 2001
    ..CMTX patients with age at onset in the first decade mostly presented non-functional mutations, suggesting that the physiological consequences of the mutations affect age at onset in CMTX...
  37. ncbi Heterozygous peripheral myelin protein 22-deficient mice are affected by a progressive demyelinating tomaculous neuropathy
    K Adlkofer
    Institute of Cell Biology, Department of Biology, Swiss Federal Institute of Technology, CH 8093 Zurich, Switzerland
    J Neurosci 17:4662-71. 1997
    ....
  38. ncbi Unusual electrophysiological findings in X-linked dominant Charcot-Marie-Tooth disease
    A Gutierrez
    Department of Neurology, Louisiana State University School of Medicine, 1542 Tulane Avenue, New Orleans, Louisiana 70112, USA
    Muscle Nerve 23:182-8. 2000
    ..This family shows that CMTX is a heterogeneous and distinctly nonuniform demyelinating polyneuropathy, the severity of which varies with sex and age. Such electrophysiological variability is unique among hereditary neuropathies...
  39. ncbi MFN2 mutation distribution and genotype/phenotype correlation in Charcot-Marie-Tooth type 2
    Kristien Verhoeven
    Peripheral Neuropathy Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology Antwerpen, Belgium
    Brain 129:2093-102. 2006
    ..In patients with a documented family history of CMT2 the frequency of MFN2 mutations was 33% indicating that MFN2 mutations are a major cause in this population...
  40. ncbi Transient, recurrent, white matter lesions in X-linked Charcot-Marie-Tooth disease with novel connexin 32 mutation
    C Oliver Hanemann
    Department of Neurology, University of Ulm, Ulm, Germany
    Arch Neurol 60:605-9. 2003
    ..This is of potential interest, as Cx32 is widely expressed in both peripheral nerve and the brain...
  41. ncbi Functional abnormalities in P0-deficient mice resemble human hereditary neuropathies linked to P0 gene mutations
    J Zielasek
    Department of Neurology, Julius Maximillians University, Wurzburg, Germany
    Muscle Nerve 19:946-52. 1996
    ..Thus, P0 -/- mice resemble severe human inherited neuropathies like Charcot-Marie-Tooth disease type 3 (Déjérine-Sottas disease) with onset early in life, whereas the P0 +/- mice may resemble the milder form, CMT1B...
  42. ncbi Transgenic mouse models of CMT1A and HNPP
    U Suter
    Department of Biology, Swiss Federal Institute of Technology, ETH Honggerberg, Zurich, Switzerland
    Ann N Y Acad Sci 883:247-53. 1999
    ..Such considerations should be taken into account in the design of potential novel treatment strategies...
  43. ncbi Variability of disease progression in a family with autosomal recessive CMT associated with a S194X and new R310Q mutation in the GDAP1 gene
    H Azzedine
    INSERM U289, Hopital de la Salpetriere, 47 Boulevard de l Hopital, 75651 Paris 13, France
    Neuromuscul Disord 13:341-6. 2003
    ..The phenotype included hoarse voice and paralysis of the diaphragm. This study shows the variability of the phenotype associated with mutations in GDAP1 gene in terms of associated signs and severity...
  44. ncbi Mutations in the ganglioside-induced differentiation-associated protein-1 (GDAP1) gene in intermediate type autosomal recessive Charcot-Marie-Tooth neuropathy
    Jan Senderek
    Department of Human Genetics, Aachen University of Technology, Germany
    Brain 126:642-9. 2003
    ..These findings fitted the definition of intermediate type CMT and further support the view that GDAP1 is vital for both, axonal integrity and Schwann cell properties...
  45. pmc Mutations in MTMR13, a new pseudophosphatase homologue of MTMR2 and Sbf1, in two families with an autosomal recessive demyelinating form of Charcot-Marie-Tooth disease associated with early-onset glaucoma
    H Azzedine
    U289 INSERM, Assistance Publique Hopitaux de Paris, Groupe Hospitalier Pitie Salpetriere, Paris, France
    Am J Hum Genet 72:1141-53. 2003
    ..MTMR13 may be important for the development of both the peripheral nerves and the trabeculum meshwork, which permits the outflow of the aqueous humor. Both of these tissues have the same embryonic origin...
  46. ncbi Duplication in chromosome 17p11.2 in Charcot-Marie-Tooth neuropathy type 1a (CMT 1a). The HMSN Collaborative Research Group
    P Raeymaekers
    Born Bunge Foundation, Department of Biochemistry, University of Antwerp UIA, Belgium
    Neuromuscul Disord 1:93-7. 1991
    ..These findings led us to propose that the duplication in 17p11.2 itself is the disease causing mutation in all the HMSN I families analyzed...
  47. pmc Homozygous defects in LMNA, encoding lamin A/C nuclear-envelope proteins, cause autosomal recessive axonal neuropathy in human (Charcot-Marie-Tooth disorder type 2) and mouse
    Annachiara De Sandre-Giovannoli
    INSERM U491, Génétique Médicale et Développement, Faculte de Medecine de la Timone, Marseille, France
    Am J Hum Genet 70:726-36. 2002
    ....
  48. pmc Mutation of FIG4 causes a rapidly progressive, asymmetric neuronal degeneration
    Xuebao Zhang
    Department of Neurology, Wayne State University School of Medicine, Detroit, MI 48201, USA
    Brain 131:1990-2001. 2008
    ..This study represents the first documentation of the natural history of CMT4J. Physical obstruction of organelle trafficking by vacuoles is a potential novel cellular mechanism of neurodegeneration...
  49. ncbi Mtmr13/Sbf2-deficient mice: an animal model for CMT4B2
    Kristian Tersar
    Institute of Cell Biology, Department of Biology, ETH Zurich, Switzerland
    Hum Mol Genet 16:2991-3001. 2007
    ....
  50. pmc A new variant of Charcot-Marie-Tooth disease type 2 is probably the result of a mutation in the neurofilament-light gene
    I V Mersiyanova
    Research Centre for Medical Genetics, Moscow, Russia
    Am J Hum Genet 67:37-46. 2000
    ..It is suggested that Gln333Pro represents a rare disease-causing mutation, which results in the CMT2 phenotype...
  51. ncbi Mutation of the SBF2 gene, encoding a novel member of the myotubularin family, in Charcot-Marie-Tooth neuropathy type 4B2/11p15
    Jan Senderek
    Department of Human Genetics, Aachen University of Technology, Aachen, Germany
    Hum Mol Genet 12:349-56. 2003
    ....
  52. ncbi Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2
    Stephan Zuchner
    Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA
    Ann Neurol 59:276-81. 2006
    ..Reports of affected families have indicated autosomal dominant and recessive forms, but the genetic cause of this disease has remained elusive...
  53. ncbi Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies
    L E Warner
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA
    Nat Genet 18:382-4. 1998
    ....
  54. ncbi Charcot-Marie-Tooth disease type 2A caused by mutation in a microtubule motor KIF1Bbeta
    C Zhao
    Department of Cell Biology and Anatomy, University of Tokyo, Hongo, Tokyo 113 0033, Japan
    Cell 105:587-97. 2001
    ..We show that CMT2A patients contain a loss-of-function mutation in the motor domain of the KIF1B gene. This is clear indication that defects in axonal transport due to a mutated motor protein can underlie human peripheral neuropathy...
  55. ncbi Multi-level regulation of myotubularin-related protein-2 phosphatase activity by myotubularin-related protein-13/set-binding factor-2
    Philipp Berger
    Institute of Cell Biology, Dept of Biology, Swiss Federal Institute of Technology ETH Hönggerberg, CH 8093 Zurich, Switzerland
    Hum Mol Genet 15:569-79. 2006
    ....
  56. ncbi Phenotypic differences between peripheral myelin protein-22 (PMP22) and myelin protein zero (P0) mutations associated with Charcot-Marie-Tooth-related diseases
    Igor Shames
    Department of Neurology and Neurosurgery, McGill University, Montreal, Canada
    J Neuropathol Exp Neurol 62:751-64. 2003
    ..These findings indicate that the various P0 and PMP22 mutants may exert their pathogenic effects in different subcellular compartments and by different mechanisms in the mammalian cell...
  57. ncbi Mutations in the neurofilament light chain gene (NEFL) cause early onset severe Charcot-Marie-Tooth disease
    A Jordanova
    Molecular Genetics Department, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Belgium
    Brain 126:590-7. 2003
    ....
  58. ncbi Charcot-Marie-Tooth disease and sleep apnoea syndrome: a family study
    M Dematteis
    , University Hospital, Grenoble, France
    Lancet 357:267-72. 2001
    ..Upper airway dysfunction, previously described in the CMT2C subtype, might be a clinical expression of the CMT1A subtype, to which familial susceptibility could predispose...
  59. ncbi The gene encoding ganglioside-induced differentiation-associated protein 1 is mutated in axonal Charcot-Marie-Tooth type 4A disease
    Ana Cuesta
    Laboratory of Genetics and Molecular Medicine, Instituto de Biomedicina, Consejo Superior de Investigaciones Cientificas CSIC, 46010 Valencia, Spain
    Nat Genet 30:22-5. 2002
    ..1. These results establish the molecular etiology of CMT4A (MIM 214400) and suggest that it may be associated with both axonal and demyelinating phenotypes...
  60. ncbi Charcot-Marie-Tooth neuropathy: clinical phenotypes of four novel mutations in the MPZ and Cx 32 genes
    V A Street
    Bloedel Hearing Center, University of Washington, Seattle, WA 98195, USA
    Neuromuscul Disord 12:643-50. 2002
    ..Mutations in the cytoplasmic domain of myelin P0 can cause clinical neuropathy. The S49P mutation in the connexin 32 gene can produce aspects of a demyelinating type of X-linked hereditary neuropathy...
  61. ncbi Molecular cell biology of Charcot-Marie-Tooth disease
    Philipp Berger
    Department of Biology, Swiss Federal Institute of Technology, Zurich, Switzerland
    Neurogenetics 4:1-15. 2002
    ....
  62. ncbi Mutations in GDAP1: autosomal recessive CMT with demyelination and axonopathy
    E Nelis
    Molecular Genetics Department, Flanders Interuniversity Institute of Biotechnology, Belgium
    Neurology 59:1865-72. 2002
    ....
  63. ncbi The CNS phenotype of X-linked Charcot-Marie-Tooth disease: more than a peripheral problem
    Robert A Taylor
    Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, USA
    Neurology 61:1475-8. 2003
  64. ncbi Real-time quantitative polymerase chain reaction. A new method that detects both the peripheral myelin protein 22 duplication in Charcot-Marie-Tooth type 1A disease and the peripheral myelin protein 22 deletion in hereditary neuropathy with liability to p
    N K Aarskog
    Department of Neurology, Haukeland University Hospital, University of Bergen, Norway
    Hum Genet 107:494-8. 2000
    ..It involves no radioisotopes and requires no post-PCR handling. In our opinion, real-time quantitative PCR is the first method of choice in diagnosing PMP22 duplication and deletion...
  65. ncbi Advances in Charcot-Marie-Tooth disease research: cellular function of CMT-related proteins, transgenic animal models, and pathomechanisms. The European CMT Consortium
    H W Muller
    Department of Neurology, Heinrich Heine University, Dusseldorf, Germany
    Neurobiol Dis 4:215-20. 1997
    ..In this minireview, we summarize the key findings presented and discuss their impact on CMT research...
  66. pmc Mitochondrial fusion and function in Charcot-Marie-Tooth type 2A patient fibroblasts with mitofusin 2 mutations
    Elizabeth A Amiott
    Department of Biochemistry, University of Utah School of Medicine, 15 N Medical Drive East, Salt Lake City, UT 84112, USA
    Exp Neurol 211:115-27. 2008
    ..We discuss our results and those of others in terms of a comprehensive model for the mechanism(s) by which mutations in MFN2 may lead to CMT2A disease...
  67. ncbi Identification of a new locus for autosomal recessive Charcot-Marie-Tooth disease with focally folded myelin on chromosome 11p15
    K B Othmane
    Division of Neurology, Duke University Medical Center, Durham, North Carolina 27710 2903, USA
    Genomics 62:344-9. 1999
    ..6-cM interval between markers D11S1331 and D11S4194. The second Tunisian CMT4B family was excluded from linkage to the new locus, demonstrating the existence of at least a third locus for the CMT4B phenotype...
  68. ncbi Reliability of clinical outcome measures in Charcot-Marie-Tooth disease
    A Solari
    Neuroepidemiology Unit, IRCCS Foundation, C Besta Neurological Institute, Via Celoria 11, 20133 Milan, Italy
    Neuromuscul Disord 18:19-26. 2008
    ..All outcome measures appear adequate for CMT assessment. Use of an immobilization device improves foot MVIC reliability, preventing biased findings in patients with greater strength...
  69. ncbi Charcot-Marie-Tooth with pyramidal signs is genetically heterogeneous: families with and without MFN2 mutations
    D Zhu
    ANZAC Research Institute, University of Sydney, Concord Hospital, NSW, Australia
    Neurology 65:496-7. 2005
  70. pmc Genetics of Charcot-Marie-Tooth disease type 4A: mutations, inheritance, phenotypic variability, and founder effect
    R Claramunt
    J Med Genet 42:358-65. 2005
  71. ncbi Functional consequences of mutations in the early growth response 2 gene (EGR2) correlate with severity of human myelinopathies
    L E Warner
    Department of Molecular and Human Genetics, Baylor College of Medicine, Hoston, TX 77030, USA
    Hum Mol Genet 8:1245-51. 1999
    ..These data provide insight into the possible disease mechanisms underlying EGR2 mutations and the reason for varying severity and differences in inheritance patterns...
  72. ncbi Demyelinating and axonal features of Charcot-Marie-Tooth disease with mutations of myelin-related proteins (PMP22, MPZ and Cx32): a clinicopathological study of 205 Japanese patients
    Naoki Hattori
    Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan
    Brain 126:134-51. 2003
    ....
  73. ncbi The phosphoinositide-3-phosphatase MTMR2 associates with MTMR13, a membrane-associated pseudophosphatase also mutated in type 4B Charcot-Marie-Tooth disease
    Fred L Robinson
    Department of Pharmacology, The University of California San Diego, La Jolla, California 92093, USA
    J Biol Chem 280:31699-707. 2005
    ..Such a mechanism would explain the strikingly similar phenotypes of patients with recessive mutations in either MTMR2 or MTMR13...
  74. ncbi Mitochondrial GTPase mitofusin 2 mutation in Charcot-Marie-Tooth neuropathy type 2A
    Kazuki Kijima
    Department of Pediatrics, Yamagata University School of Medicine, 2 2 2 Iida nishi, Yamagata 990 9585, Japan
    Hum Genet 116:23-7. 2005
    ..Formation of a mitochondrial network would be required to maintain the functional peripheral nerve axon...
  75. ncbi DNA duplication associated with Charcot-Marie-Tooth disease type 1A
    J R Lupski
    Institute for Molecular Genetics, Baylor College of Medicine, Houston, Texas 77030
    Cell 66:219-32. 1991
    ..We have demonstrated that failure to recognize the molecular duplication can lead to misinterpretation of marker genotypes for affected individuals, identification of false recombinants, and incorrect localization of the disease locus...
  76. ncbi Clinical phenotypes of different MPZ (P0) mutations may include Charcot-Marie-Tooth type 1B, Dejerine-Sottas, and congenital hypomyelination
    L E Warner
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA
    Neuron 17:451-60. 1996
    ..Furthermore, we hypothesize the differences in clinical severity seen with mutations in MPZ are related to the type of mutation and its subsequent effect on protein function (i.e., loss of function versus dominant negative)...
  77. ncbi Therapeutic administration of progesterone antagonist in a model of Charcot-Marie-Tooth disease (CMT-1A)
    Michael W Sereda
    Max Planck Institute of Experimental Medicine, Department of Neurogenetics, Hermann Rein Str 3, D 37075 Gottingen, Germany
    Nat Med 9:1533-7. 2003
    ..Taken together, these data provide proof of principle that the progesterone receptor of myelin-forming Schwann cells is a promising pharmacological target for therapy of CMT-1A...
  78. ncbi Poor tolerability of high dose ascorbic acid in a population of genetically confirmed adult Charcot-Marie-Tooth 1A patients
    C Toth
    Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada
    Acta Neurol Scand 120:134-8. 2009
    ..Preclinical studies have suggested that ascorbic acid (AA) treatment in a mouse model of Charcot-Marie-Tooth type 1A (CMT1A) improves motor function and prolongs lifespan...
  79. ncbi A new quantitative PCR multiplex assay for rapid analysis of chromosome 17p11.2-12 duplications and deletions leading to HMSN/HNPP
    Christian T Thiel
    Institute of Human Genetics, University of Erlangen Nuremberg, Schwabachanlage 10, 91054 Erlangen, Germany
    Eur J Hum Genet 11:170-8. 2003
    ..Thus, this method shows superior sensitivity to microsatellite analysis and has the additional advantage of being a fast and uniform assay for quantitative analysis of both CMT1A and HNPP...
  80. ncbi An epidemiological genetic study of Charcot-Marie-Tooth disease in Western Japan
    Saiko Kurihara
    Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Yonago, Japan
    Neuroepidemiology 21:246-50. 2002
    ..To identify the occurrence of mildly affected CMT, the exhaustive region-matched and family study was necessary...
  81. ncbi Correlation between clinical/neurophysiological findings and quality of life in Charcot-Marie-Tooth type 1A
    Luca Padua
    Institute of Neurology, Universita Cattolica del Sacro Cuore, Rome, Italy
    J Peripher Nerv Syst 13:64-70. 2008
    ..Both the PCS and MCS were abnormal also in this cohort, compared with the Italian population at large. In particular, the ability to ambulate independently as well as toe and heel walk correlated well with QoL measures in our patients...
  82. ncbi Preserved myelin integrity and reduced axonopathy in connexin32-deficient mice lacking the recombination activating gene-1
    I Kobsar
    Department of Neurology, University of Wurzburg, Wurzburg, Germany
    Brain 126:804-13. 2003
    ..Since both cx32- and P0 deficiency lead to similar immunopathogenic processes, we conclude that immune-mediated demyelination may be a feature common to many CMT-like neuropathies independent of the genetic origin...
  83. ncbi Increased prevalence of obstructive sleep apnoea in patients with Charcot-Marie-Tooth disease: a case control study
    R Dziewas
    Department of Neurology, University Hospital of Munster, Albert Schweitzer Strasse 33, 48129 Munster, Germany
    J Neurol Neurosurg Psychiatry 79:829-31. 2008
    ..Pathophysiologically, one may assume that CMT1 related pharyngeal neuropathy increases the collapsibility of the upper airway which in turn leads to recurring obstructive respiratory events...
  84. ncbi [Mutations in the mitofusin 2 gene are the most common cause of Charcot-Marie-Tooth type 2 disease]
    Ewa Sołtysińska
    Zespół Badawczo Leczniczy Chorób Nerwowo Mieśniowych, Instytut Medycyny Doświadczalnej i Klinicznej im M Mossakowskiego Polskiej Akademii Nauk, Warszawa
    Neurol Neurochir Pol 41:350-4. 2007
    ..As MFN2 gene mutations are the most common cause of autosomal dominant CMT2 disease (33% of cases), MFN2 gene testing may be considered a diagnostic test for CMT2...
  85. ncbi Two Spanish families with Charcot-Marie-Tooth type 2A: clinical, electrophysiological and molecular findings
    I Banchs
    Molecular Diagnosis Center of Inherited Diseases, Institut d Investigacions Biomèdiques de Bellvitge IDIBELL, L Hospitalet de Llobregat, Barcelona, Spain
    Neuromuscul Disord 18:974-8. 2008
    ..Population studies of mutations in MFN2 should be undertaken to discover the real frequencies in the Mediterranean area...
  86. ncbi Mutation analysis of the small heat shock protein 27 gene in chinese patients with Charcot-Marie-Tooth disease
    Beisha Tang
    Department of Neurology, Xiangya Hospital, Central South University, Changsha, People s Republic of China
    Arch Neurol 62:1201-7. 2005
    ..Recently, mutations in small heat shock protein 27 (Hsp27) were reported to cause CMT disease type 2F and distal hereditary motor neuropathy...
  87. ncbi Disorders of pulmonary function, sleep, and the upper airway in Charcot-Marie-Tooth disease
    Loutfi S Aboussouan
    Department of Pulmonary and Critical Care Medicine, Cleveland Clinic Foundation, 26900 Cedar Road, Suite 325 S, Beachwood, OH 44122, USA
    Lung 185:1-7. 2007
    ..The risk of progression to bilateral vocal cord dysfunction in CMT and the risk of aspiration with laryngeal neuropathy may limit the therapeutic options available for vocal cord paralysis...
  88. ncbi Myotubularin-related 2 protein phosphatase and neurofilament light chain protein, both mutated in CMT neuropathies, interact in peripheral nerve
    Stefano C Previtali
    Neuropathology Unit, Department of Neurology, San Raffaele Scientific Institute, 20132 Milan, Italy
    Hum Mol Genet 12:1713-23. 2003
    ....
  89. ncbi Coincidence of two genetic forms of Charcot-Marie-Tooth disease in a single family
    C Verny
    INSERM U289, Hopital Pitie Salpetriere, 47 bd de l Hopital, 75651, Paris Cedex 13, France
    Neurology 63:1527-9. 2004
    ..One had related parents, and there were no other affected relatives, suggesting an autosomal recessive mode of inheritance. Molecular studies showed that a de novo duplication in 17p11.2 and a second mutation in MTMR2 were present...
  90. ncbi SET binding factor 2 (SBF2) mutation causes CMT4B with juvenile onset glaucoma
    R Hirano
    Department of Neurology and Geriatrics, Kagoshima University School of Medicine, Kagoshima City, Kagoshima, Japan
    Neurology 63:577-80. 2004
    ..The consistent phenotypic features associated with SBF2 mutations are early-onset demyelinating neuropathy, myelin folding, and markedly decreased motor nerve conduction velocities; glaucoma associates with SBF2 nonsense mutations...
  91. ncbi Ascorbic acid treatment corrects the phenotype of a mouse model of Charcot-Marie-Tooth disease
    Edith Passage
    Institut National de la Santé et de la Recherche Médicale UMR491, IPHM, Faculte de Medecine de la Timone, 27 Bd J Moulin, 13385 Marseille Cedex 5, France
    Nat Med 10:396-401. 2004
    ..As ascorbic acid has already been approved by the FDA for other clinical indications, it offers an immediate therapeutic possibility for patients with the disease...
  92. ncbi Crystal structure of a phosphoinositide phosphatase, MTMR2: insights into myotubular myopathy and Charcot-Marie-Tooth syndrome
    Michael J Begley
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Mol Cell 12:1391-402. 2003
    ..Finally, the MTMR2 structure will serve as a model for other members of the myotubularin family and provide a framework for understanding the mechanism whereby mutations in these proteins lead to disease...
  93. pmc A locus for an axonal form of autosomal recessive Charcot-Marie-Tooth disease maps to chromosome 1q21.2-q21.3
    A Bouhouche
    INSERM U 289, Federation de Neurologie, Hopital de la Salpetriere, Bâtiment Nouvelle Pharmacie, Paris, France
    Am J Hum Genet 65:722-7. 1999
    ..7 cM. In addition, the P0 gene, an attractive candidate because of both its location on chromosome 1q and its role in myelin structure, was excluded by physical mapping and direct sequencing...
  94. pmc Dominant intermediate Charcot-Marie-Tooth type C maps to chromosome 1p34-p35
    Albena Jordanova
    Molecular Genetics Department, Flanders Interuniversity Institute for Biotechnology, Antwerp, Belgium
    Am J Hum Genet 73:1423-30. 2003
    ..3-cM linkage interval flanked by markers D1S2787 and D1S2830. The functional and positional candidate genes, Syndecan 3 (SDC3), and lysosomal-associated multispanning membrane protein 5 (LAPTM5) were excluded for pathogenic mutations...
  95. ncbi Emerging pathways for hereditary axonopathies
    Stephan Zuchner
    Center for Human Genetics, Duke University Medical Center, 595 LaSalle Street, Box 3445 DUMC, Durham, NC 27710, USA
    J Mol Med (Berl) 83:935-43. 2005
    ..This review attempts to cross the traditional clinical classifications in order to draw an emerging picture of common pathways between causative genes, providing a different perspective of this rapidly growing scientific field...
  96. ncbi Quality of life in patients with Charcot-Marie-Tooth disease
    P Vinci
    Department of Physical Medicine and Rehabilitation, University La Sapienza, Rome, Italy
    Neurology 65:922-4. 2005
    ....
  97. pmc Membrane association of myotubularin-related protein 2 is mediated by a pleckstrin homology-GRAM domain and a coiled-coil dimerization module
    Philipp Berger
    Institute of Cell Biology and Institute for Molecular Biology and Biophysics, Department of Biology, Swiss Federal Institute of Technology, Eidgenossische Technische Hochschule Honggerberg, CH 8093 Zurich, Switzerland
    Proc Natl Acad Sci U S A 100:12177-82. 2003
    ..Our data indicate that phosphoinositide-protein interactions, as well as protein-protein interactions, are necessary for the correct regulation of MTMR2...
  98. ncbi An animal model for Charcot-Marie-Tooth disease type 4B1
    Sonja Bonneick
    Institute of Cell Biology, Department of Biology, Swiss Federal Institute of Technology, Zurich, Switzerland
    Hum Mol Genet 14:3685-95. 2005
    ....
  99. pmc Charcot-Marie-Tooth neuropathy type 2A: novel mutations in the mitofusin 2 gene (MFN2)
    Kathrin Engelfried
    Department of Human Genetics, Ruhr University Bochum, Germany
    BMC Med Genet 7:53. 2006
    ..Charcot-Marie-Tooth neuropathies are a group of genetically heterogeneous diseases of the peripheral nervous system. Mutations in the MFN2 gene have been reported as the primary cause of Charcot-Marie-Tooth disease type 2A...
  100. ncbi Mechanisms of disease: a molecular genetic update on hereditary axonal neuropathies
    Stephan Zuchner
    Department of Psychiatry, Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA
    Nat Clin Pract Neurol 2:45-53. 2006
    ..The known CMT2-related genes represent key players in these pathways, however, and are likely to provide powerful tools for identifying targets for future therapeutic intervention...
  101. ncbi Charcot-Marie-Tooth disease: an update
    Michael E Shy
    Department of Neurology, Wayne State University, School of Medicine, Detroit, Michigan 48201, USA
    Curr Opin Neurol 17:579-85. 2004
    ..Currently, mutations in multiple different genes expressed in Schwann cells and neurons cause a variety of overlapping clinical phenotypes...

Research Grants64

  1. Genetics of the Neuromuscular Junction: Mechanisms and Disease Models
    Robert W Burgess; Fiscal Year: 2013
    ....
  2. In vivo analysis of the mechanisms of axon transport.
    Catherine M Drerup; Fiscal Year: 2011
    ..Additionally, they will establish zebrafish as a model system that can be used to investigate the function of genes associated with axonal diseases to determine if disease etiology lies in interruptions of this basic cellular process. ..
  3. Optimization of HDAC6 Inhibitors in the Treatment of CMT
    Ludo Van Den Bosch; Fiscal Year: 2013
    ....
  4. Alternate pore isoforms of a mechanotransducing ion channel
    Maurice J Kernan; Fiscal Year: 2013
    ..Thus, findings from the TRPN channel variants, and their role in insect mechanosensory cilia may be very broadly applicable. ..
  5. Structural and Functional Studies of the Sac Family Phosphoinositide Phosphatases
    Yuxin Mao; Fiscal Year: 2013
    ....
  6. Neuronal Cell Cycle and Survival
    Nicholas E Baker; Fiscal Year: 2013
    ....
  7. Allosteric Regulation of SNAREs and the Rab GEF Mon1 by Phosphoinositides
    Rutilio A Fratti; Fiscal Year: 2013
    ..The proposed study will define how the composition of the vacuolar membrane regulates SNARE and Mon1 function and will give us clues about the relationship between lipid modification and human health and disease. ..
  8. MICROTUBULE MOTORS STUDIED ON A MOLECULAR SCALE
    Steven M Block; Fiscal Year: 2010
    ....
  9. Extra-translational roles of aminoacyl tRNA synthetases in connection to disease
    Xiang Lei Yang; Fiscal Year: 2013
    ..The knowledge we gain in this study will also shed light on other neurological diseases such as Amyotrophic Lateral Sclerosis (Lou Gehrig's disease) and Parkinson's disease. ..
  10. Comprehensive mutation detection for Neuromuscular disorders: Bringing new techno
    Madhuri R Hegde; Fiscal Year: 2010
    ..This project will develop the technology and protocols leading to a novel highly sensitive, rapid and reliable diagnostic tool for enhanced molecular testing for inherited NMDs. ..
  11. Gene interaction in development and disease
    Miriam H Meisler; Fiscal Year: 2013
    ..The proposed experiments will integrate genetic analysis of pathogenic human mutations with functional dissection of PI(3,5)P2 activity to advance our understanding of the role of this pathway in human disease. ..
  12. Quantitative MRI of the Human Peripheral Nervous System In Vivo
    RICHARD DARRELL DORTCH; Fiscal Year: 2013
    ..g., diabetic neuropathy) as well as in diseases that affect myelin and/or axons within the central nervous system (e.g., multiple sclerosis). ..
  13. Genetic analyses of axon transport and microtubule dynamics in Zebrafish
    Alex Nechiporuk; Fiscal Year: 2013
    ....
  14. Assembly and Axonal Transport of Neurofilaments
    Anthony Brown; Fiscal Year: 2013
    ..The mechanisms that regulate neurofilament pausing are likely targets for disease processes that lead to excessive accumulation of neurofilaments in axons. ..
  15. Tau causes neurodegeneration in vivo through mitochondrial disruption
    BRIAN MICHAEL DUBOFF; Fiscal Year: 2010
    ..Post-mortem tissue analysis suggests mitochondria may be involved in Alzheimer's disease, making mitochondria a strong candidate for disease research. ..
  16. Regulatory subunits of PP2A in neuronal function
    Stefan Strack; Fiscal Year: 2011
    ..These studies are significant in that they advance our understanding of the critical regulatory enzyme PP2A with the ultimate goal of better therapies for several neurodegenerative disorders. ..
  17. Structure and Function of Retinal Ganglion Cell Gap Junctions
    Bela Volgyi; Fiscal Year: 2011
    ..Therefore, it is likely that defects in retinal gap junctions will lead to retinopathies associated with impairment of signaling and adaptation. ..
  18. Genomic Studies in Charcot-Marie-Tooth Disease
    Stephan Zuchner; Fiscal Year: 2013
    ..Importantly, related axonal neuropathies, such as diabetic neuropathy, drug-induced neuropathies and degenerative diseases of motor and sensory neurons will greatly benefit from the results of such studies. ..
  19. Visualization of In Vivo Myelin Architecture Using Nonlinear Microscopy
    Hyungsik Lim; Fiscal Year: 2013
    ..Moreover, our development may also have a clinical relevance as a diagnostic for demyelination diseases. ..
  20. Cellular events in heritable peripheral neuropathies
    Lucia Notterpek; Fiscal Year: 2013
    ..abstract_text> ..
  21. Inherited Neurophathies Consortium (RDCRC)
    Michael E Shy; Fiscal Year: 2013
    b>Charcot Marie Tooth disease (CMT) is the eponym for heritable peripheral neuropathy. These are among the most common inherited neuromuscular diseases, affecting approximately 1 in 2500 people...
  22. Molecular pathogenesis of SIMPLE in Charcot-Marie-Tooth disease
    MING HIN LEE; Fiscal Year: 2010
    ..Therefore, this project will examine the molecular basis of CMT in hopes of providing better treatments for these patients. ..
  23. Milton and the Transport of Mitochondria
    Thomas L Schwarz; Fiscal Year: 2012
    ..Our studies are designed to determine the normal means by which mitochondria are distributed in cells and thereby gain insights into potential pathological mechanisms, including the role of mitochondrial movement in responses to stress. ..
  24. Phosphoinositide Phosphatases
    Jack E Dixon; Fiscal Year: 2013
    ..We are characterizing these mice phenotypically and will combine a series of systemic and biochemical approaches to study the role of PTPMT1 in cellular and whole animal contexts. ..
  25. An Animal Model of LRSAM1 Peripheral Neuropathy
    Robert W Burgess; Fiscal Year: 2013
    ....
  26. SVIP and CMT1A
    Jun Li; Fiscal Year: 2013
    ..Finally, knowledge derived from this study should have broad implications in other neurodegenerative disorders with abnormal protein aggregates. ..
  27. Molecular basis of Scapuloperoneal SMA and Charcot-Marie-Tooth disease type 2C
    Han Xiang Deng; Fiscal Year: 2013
    ....
  28. Validation of a Disease-Specific Instrument for Pediatric Inherited Neuropathy
    Sindhu Ramchandren; Fiscal Year: 2013
    ..Success in achieving the proposed aims would lead to the identification of validated outcome measures for future clinical trials as well as the expertise needed by the PI to lead early phase clinical trials in pediatric CMT. ..
  29. Mechanisms of Kinesin Regulation
    Sarah E Rice; Fiscal Year: 2013
    ..abstract_text> ..
  30. Gating and Regulation of Connexin Hemichannels
    JORGE ENRIQUE CONTRERAS; Fiscal Year: 2013
    ....
  31. Function of Myotubularin Phosphoinositide Phosphatase in Morphogenesis
    Amy A Kiger; Fiscal Year: 2012
    ..This research will provide insights on phosphoinositide pathways important for cell spatial regulation and disease. ..
  32. Mechanisms of dynamin family GTPases
    Mark A Lemmon; Fiscal Year: 2010
    ..We will also investigate the structural basis for cardiolipin recognition. Together, these studies promise to provide valuable insight into the mechanisms of action of these important large GTPases. ..
  33. Drug Screening Assays for Charcot-Marie-Tooth Disease
    JOHN P SVAREN; Fiscal Year: 2012
    ..A series of validation assays are proposed to determine if the reporter assays are appropriately regulated, and such assays will be adapted for high throughput screening at the NIH Chemical Genomics Center. ..
  34. FUNCTION AND REGULATION OF INTERCELLULAR COMMUNICATION
    David L Paul; Fiscal Year: 2010
    ..We propose to define the separate and interacting roles of connexins in myelination and why mutations cause disease using a combination of targeted gene ablation and functional analysis of connexin channel activity. '. ..
  35. AUTOMATED DETECTION OF GENE DUPLICATIONS OR DELETIONS
    Fatima Merchant; Fiscal Year: 2005
    ..This will provide a screening test and eventually a diagnostic test for those individuals with perhaps mild phenotypes, such as learning disabilities. ..
  36. Structure, Folding, and Misfolding of PMP22
    Charles R Sanders; Fiscal Year: 2012
    ..abstract_text> ..
  37. X-LINKED CHARCOT-MARIE TOOTH DISEASE
    Thaddeus Kelly; Fiscal Year: 1990
    ..During the course of these studies, pedigree data and DNA samples from selected families with other forms of CMT will be collected for future mapping studies...
  38. NEURONAL DEVELOPMENT INTERACTION AND ORGANIZATION
    Michael Bennett; Fiscal Year: 2000
    ....
  39. GENETIC ANALYSIS OF CHARCOT-MARIE-TOOTH DISEASE
    PHILLIP CHANCE; Fiscal Year: 1992
    ..A regional gene linkage map of chromosome 1 is of general scientific interest and will provide a useful tool to study many human disorders in this region...
  40. The Post-Transcriptional Regulation of Peripheral Myelin Protein 22 by MicroRNAs
    JONATHAN VERRIER; Fiscal Year: 2009
    ..At the conclusion of these experiments, I hope to reveal novel mechanisms governing the regulation of PMP22 that may provide new therapeutic targets for associated disease states. ..
  41. AUTOMATED DETECTION OF GENE DUPLICATIONS OR DELETIONS
    Fatima Merchant; Fiscal Year: 2000
    ..Thus, commercialization of the technology developed under this project will occur quickly. ..
  42. Structure/Function Analysis of Low pl Connexin Isoforms
    ELLIOT HERTZBERG; Fiscal Year: 2003
    ..Establishing the basis of connexin charge alteration will introduce a new player in chemical modification of proteins and their properties. ..
  43. The Role of Connexin32 in the Pathogenesis of CMTX
    Steven Scherer; Fiscal Year: 2006
    ....
  44. Molecular pathology of deafness due to mutation in PMP22
    MARGARET KOVACH; Fiscal Year: 2004
    ..abstract_text> ..
  45. Connexins in Nerve Regeneration and Inherited Neuropathy
    Charles Abrams; Fiscal Year: 2009
    ..The experiments outlined in this proposal should play a key role in understanding the role of Cx32 in the Schwann cell and how mutations in Cx32 lead to inherited peripheral neuropathy. ..
  46. Basis of Voltage & Chemical Gating in Connexin Channels
    MICHAEL PULJUNG; Fiscal Year: 2002
    ..Once the molecular basis of gating is identified, specific residues may be used as targets for rationale drug design to treat illnesses like CMTX. ..
  47. STRUCTURE-FUNCTION OF CONNEXIN PORES
    Andrew Harris; Fiscal Year: 2009
    ..In the present proposal, this analysis will be applied to Cx32 and Cx26, defects in which cause X-linked Charcot-Marie-Tooth disease neuropathy and sensorineural deafness, respectively. ..
  48. CONNEXIN32 MUTATIONS IN CHARCOT-MARIE-TOOTH-X DISEASE
    LINDA MUSIL; Fiscal Year: 2004
    ..These studies will elucidate the causes of phenotypic diversity in CMTX as well as provide the first molecular insights into the quality control mechanisms that govern the fidelity of connexin assembly into gap junctional channels. ..
  49. MYELIN PO PROTEIN--EXPRESSION/SORTING AND ADHESION
    Marie Filbin; Fiscal Year: 1992
    ..Such information is critical in understanding the basic mechanism and pathology of any peripheral neuropathy which involves demyelination and remyelination e.g., Charcot-Marie-Tooth disease...
  50. 2008 Myelin Gordon Research Conference
    Wendy Macklin; Fiscal Year: 2007
    ..This highlights the potential clinical implications for our investigations on myelination and remyelination. [unreadable] [unreadable] [unreadable]..
  51. CMT Peripheral Neuropathy: IV. Genes and Pathogenesis
    JAMES LUPSKI; Fiscal Year: 2005
    ..abstract_text> ..
  52. HUMAN NEUROMUSCULAR DISEASES
    David Pleasure; Fiscal Year: 2001
    ..The Administrative Core will help- with fiscal management, support the operations of the External and Internal Review Committees, and includes a Javits Junior Clinical Investigatorship. ..
  53. GENETIC ANALYSIS OF CHARCOT-MARIE TOOTH SYNDROME
    Roger Lebo; Fiscal Year: 1990
    ..Polymorphic restriction fragments closely linked to the disease locus will be used for prenatal diagnosis of at-risk fetuses. Ultimately identification of the defective CMT gene could lead to more effective treatment..
  54. Folding and Misfolding of PMP22
    CHARLES SANDERS; Fiscal Year: 2005
    ..Moreover, these studies may lead directly to the formulation of therapeutic strategies for CMTD which are based upon modulating the efficiency of productive PMP22 folding/trafficking. ..
  55. Connexin 32 Mutations in X-Linked CMT
    Charles Abrams; Fiscal Year: 2009
    ..abstract_text> ..
  56. Kinetic Discrimination of Substrates by the Ribosomal Biosynthetic Machinery
    PHILIP EFFRAIM; Fiscal Year: 2009
    ..Further elucidation of the selection ability of the translation machinery will help us understand how these malfunctions are handled by the translation machinery, and will perhaps reveal other important links to pathology. ..
  57. Gap Junction Channels Formation and Gating
    Feliksas Bukauskas; Fiscal Year: 2007
    ..Abnormalities in GJ channels play a key role in generating cardiac arrhythmias, uterine malfunction, epileptic seizures and malignant cell growth. ..
  58. The role of microRNAs in peripheral myelin formation and maintenance
    Rajeshwar Awatramani; Fiscal Year: 2009
    b>Charcot Marie Tooth disease (CMT), in all its forms, is the most common inherited peripheral neuropathy often characterized by severe demyelination in the peripheral nervous system...
  59. PO-Mediated Signaling and Myelination
    Jack Lilien; Fiscal Year: 2006
    ..abstract_text> ..
  60. CMT DISEASE--LOCALIZATION AND CLASSIFICATION OF TYPE 2
    Jeffery Vance; Fiscal Year: 1999
    ..Insight into the pathways and defects leading to these disorders will not only provide information towards the pathophysiology of neuropathy, but to genes that are important to normal axonal function and physiology as well. ..
  61. Early and Late Onset CMT1B
    Michael E Shy; Fiscal Year: 2010
    ..Human mutations in MPZ give rise to peripheral demyelinating neuropathies, Charcot Marie Tooth disease type IB (CMT1B)...
  62. MOLECULAR STUDIES IN C/M/T DISEASE TYPE 4 B AND C
    Kamel Ben Othmane; Fiscal Year: 2001
    ..The Direct selection technique will subsequently be used to construct a transcription map in the region allowing for candidate genes to be tested for mutations. ..
  63. Characterization of a novel CNS Specific connexin, Cx29
    BRUCE ALTEVOGT; Fiscal Year: 2003
    ..Mutations in Cx32 are responsible for the second most common inherited peripheral neuropathy, X-linked Charcot Marie Tooth disease (CMTX)...
  64. How do Cx32 and Cx47 mutants cause CNS demyelination?
    JENNIFER ORTHMAN; Fiscal Year: 2007
    ..This work should elucidate the molecular composition of gap junction channels that couple astrocytes and oligodendrocytes. [unreadable] [unreadable]..