Inverted formin 2-related Charcot-Marie-Tooth disease: extension of the mutational spectrum and pathological findings in Schwann cells and axons

2015 ◽  
Vol 20 (1) ◽  
pp. 52-59 ◽  
Author(s):  
Andreas Roos ◽  
Joachim Weis ◽  
Rudolf Korinthenberg ◽  
Henry Fehrenbach ◽  
Martin Häusler ◽  
...  
Keyword(s):  
Schwann Cells ◽  
Pathological Findings ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Mutational Spectrum ◽  
Disease Extension ◽  
Tooth Disease

MicroRNAs as Biomarkers of Charcot-Marie-Tooth Disease Type 1A

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012266
Author(s):  
Hongge Wang ◽  
Matthew Davison ◽  
Kathryn Wang ◽  
Tai-he Xia ◽  
Katherine M. Call ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Schwann Cells ◽  
Motor Nerve ◽  
Disease Type ◽  
Class Iii ◽  
Protein Biomarkers ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Compound Muscle Action Potentials ◽  
Tooth Disease

Objective:To determine if microRNA’s (miR) are elevated in the plasma of individuals affected by the inherited peripheral neuropathy Charcot-Marie-Tooth Disease, type 1A (CMT1A), miR profiling was employed to compare control and CMT1A plasma.Methods:We performed a screen of CMT1A and control plasma samples to identify miRs that are elevated in CMT1A using next generation sequencing, followed by validation of selected miRs by quantitative PCR, and correlation with protein biomarkers and clinical data: Rash-modified CMT Examination and Neuropathy Scores (CMTES-R and CMTNS-R), ulnar compound muscle action potentials (CMAP), and motor nerve conduction velocities (MNCV).Results:After an initial pilot screen, a broader screen confirmed elevated levels of several muscle-associated miRNAs (miR1, -133a, -133b, and -206, known as myomiRs) along with a set of miRs that are highly expressed in Schwann cells of peripheral nerve. Comparison to other candidate biomarkers for CMT1A (e.g. Neurofilament L, NfL) measured on the same sample set shows a comparable elevation of several miRs (e.g. miR133a, -206, -223) and ability to discriminate cases from controls. NfL levels were most highly correlated with miR133a. In addition, the putative Schwann cell miRs (e.g. miR223, -199a, -328, -409, and -431) correlate with the recently described TMPRSS5 protein biomarker that is most highly expressed in Schwann cells and also elevated in CMT1A plasma.Conclusions:These studies identify a set of miRs that are candidate biomarkers for clinical trials in CMT1A. Some of the miRs may reflect Schwann cell processes that underlie the pathogenesis of the disease.Classification of Evidence:This study provides Class III evidence that a set of plasma miRs are elevated in patients with CMT1A.

scholarly journals Resetting translational homeostasis restores myelination in Charcot-Marie-Tooth disease type 1B mice

2013 ◽  
Vol 210 (4) ◽  
pp. 821-838 ◽  
Author(s):  
Maurizio D’Antonio ◽  
Nicolò Musner ◽  
Cristina Scapin ◽  
Daniela Ungaro ◽  
Ubaldo Del Carro ◽  
...  
Keyword(s):  
Schwann Cells ◽  
Therapeutic Strategy ◽  
Terminal Differentiation ◽  
Motor Deficit ◽  
Demyelinating Neuropathy ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Unfolded Protein ◽  
Protein Response ◽  
Tooth Disease

P0 glycoprotein is an abundant product of terminal differentiation in myelinating Schwann cells. The mutant P0S63del causes Charcot-Marie-Tooth 1B neuropathy in humans, and a very similar demyelinating neuropathy in transgenic mice. P0S63del is retained in the endoplasmic reticulum of Schwann cells, where it promotes unfolded protein stress and elicits an unfolded protein response (UPR) associated with translational attenuation. Ablation of Chop, a UPR mediator, from S63del mice completely rescues their motor deficit and reduces active demyelination by half. Here, we show that Gadd34 is a detrimental effector of CHOP that reactivates translation too aggressively in myelinating Schwann cells. Genetic or pharmacological limitation of Gadd34 function moderates translational reactivation, improves myelination in S63del nerves, and reduces accumulation of P0S63del in the ER. Resetting translational homeostasis may provide a therapeutic strategy in tissues impaired by misfolded proteins that are synthesized during terminal differentiation.

Overexpression of ErbB2 and ErbB3 receptors in Schwann cells of patients with Charcot–Marie–Tooth disease type 1A

2006 ◽  
Vol 33 (3) ◽  
pp. 342-349 ◽  
Author(s):  
Roberto Massa ◽  
Camilla Palumbo ◽  
Tiziana Cavallaro ◽  
Maria Beatrice Panico ◽  
Roberto Bei ◽  
...  
Keyword(s):  
Schwann Cells ◽  
Disease Type ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease

scholarly journals The Mutational Spectrum in a Cohort of Charcot-Marie-Tooth Disease Type 2 among the Han Chinese in Taiwan

PLoS ONE ◽  
2011 ◽  
Vol 6 (12) ◽  
pp. e29393 ◽  
Author(s):  
Kon-Ping Lin ◽  
Bing-Wen Soong ◽  
Chih-Chao Yang ◽  
Li-Wen Huang ◽  
Ming-Hong Chang ◽  
...  
Keyword(s):  
Han Chinese ◽  
Disease Type ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Mutational Spectrum ◽  
Tooth Disease

scholarly journals Ndrg1-Deficient Mice Exhibit a Progressive Demyelinating Disorder of Peripheral Nerves

2004 ◽  
Vol 24 (9) ◽  
pp. 3949-3956 ◽  
Author(s):  
Tomohiko Okuda ◽  
Yujiro Higashi ◽  
Koichi Kokame ◽  
Chihiro Tanaka ◽  
Hisato Kondoh ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Schwann Cells ◽  
Peripheral Nerves ◽  
Sensory Neuropathy ◽  
Disease Type ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Hind Limbs ◽  
Deficient Mice ◽  
Tooth Disease

ABSTRACT NDRG1 is an intracellular protein that is induced under a number of stress and pathological conditions, and it is thought to be associated with cell growth and differentiation. Recently, human NDRG1 was identified as a gene responsible for hereditary motor and sensory neuropathy-Lom (classified as Charcot-Marie-Tooth disease type 4D), which is characterized by early-onset peripheral neuropathy, leading to severe disability in adulthood. In this study, we generated mice lacking Ndrg1 to analyze its function and elucidate the pathogenesis of Charcot-Marie-Tooth disease type 4D. Histological analysis showed that the sciatic nerve of Ndrg1-deficient mice degenerated with demyelination at about 5 weeks of age. However, myelination of Schwann cells in the sciatic nerve was normal for 2 weeks after birth. Ndrg1-deficient mice showed muscle weakness, especially in the hind limbs, but complicated motor skills were retained. In wild-type mice, NDRG1 was abundantly expressed in the cytoplasm of Schwann cells rather than the myelin sheath. These results indicate that NDRG1 deficiency leads to Schwann cell dysfunction, suggesting that NDRG1 is essential for maintenance of the myelin sheaths in peripheral nerves. These mice will be used for future analyses of the mechanisms of myelin maintenance.

Pathological findings in the x-linked form of Charcot-Marie-Tooth disease: a morphometric and ultrastructural analysis

2001 ◽  
Vol 101 (2) ◽  
pp. 129-139 ◽  
Author(s):  
Angelika F. Hahn ◽  
Peter J. Ainsworth ◽  
Charles F. Bolton ◽  
Juan M. Bilbao ◽  
Jean-Michel Vallat
Keyword(s):  
Ultrastructural Analysis ◽  
Pathological Findings ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease
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