Read by QxMD icon Read

Charcot + marie

Jennifer Pasquier, Mark Spurgeon, Martina Bradic, Binitha Thomas, Amal Robay, Omar Chidiac, Marie-Joe Dib, Rebal Turjoman, Alexandra Liberska, Michelle Staudt, Khalid A Fakhro, Robert Menzies, Amin Jayyousi, Mahmoud Zirie, Jassim Al Suwaidi, Rayaz A Malik, Talal Talal, Arash Rafii, Jason Mezey, Juan Rodriguez-Flores, Ronald G Crystal, Charbel Abi Khalil
AIM: To assess whether DNA methylation of monocytes play a role in the development of acute diabetic Charcot foot (CF). PATIENTS & METHODS: We studied the whole methylome (WM) of circulating monocytes in 18 patients with Type 2 diabetes (T2D) and acute CF, 18 T2D patients with equivalent neuropathy and 18 T2D patients without neuropathy, using the enhanced reduced representation bisulfite sequencing technique. RESULTS & CONCLUSION: WM analysis demonstrated that CF monocytes are differentially methylated compared with non-CF monocytes, in both CpG-site and gene-mapped analysis approaches...
February 2019: Epigenomics
Guy M Lenk, Ian R Berry, Chloe A Stutterd, Moira Blyth, Lydia Green, Gayatri Vadlamani, Daniel Warren, Ian Craven, Miriam Fanjul-Fernandez, Victoria Rodriguez-Casero, Paul J Lockhart, Adeline Vanderver, Cas Simons, Susan Gibb, Simon Sadedin, Susan M White, John Christodoulou, Olga Skibina, Jonathan Ruddle, Tiong Y Tan, Richard J Leventer, John H Livingston, Miriam H Meisler
The lipid phosphatase gene FIG. 4 is responsible for Yunis-Varón Syndrome and Charcot-Marie-Tooth Disease Type 4J, a peripheral neuropathy. We now describe four families with FIG. 4 variants and prominent abnormalities of CNS white matter (leukoencephalopathy), with onset in early childhood, ranging from severe hypomyelination to mild undermyelination, in addition to peripheral neuropathy. Affected individuals inherited biallelic FIG. 4 variants from heterozygous parents. Cultured fibroblasts exhibit enlarged vacuoles characteristic of FIG...
February 10, 2019: Human Mutation
Dana M Bis-Brewer, Matt C Danzi, Stefan Wuchty, Stephan Züchner
Inherited axonopathies represent a spectrum of disorders unified by the common pathological mechanism of length-dependent axonal degeneration. Progressive axonal degeneration can lead to both Charcot-Marie-Tooth type 2 (CMT2) and Hereditary Spastic Paraplegia (HSP) depending on the affected neurons: peripheral motor and sensory nerves or central nervous system axons of the corticospinal tract and dorsal columns, respectively. Inherited axonopathies display an extreme degree of genetic heterogeneity of Mendelian high-penetrance genes...
February 8, 2019: Scientific Reports
João P L Coelho, Matthias Stahl, Nicolas Bloemeke, Kevin Meighen-Berger, Carlos Piedrafita Alvira, Zai-Rong Zhang, Stephan A Sieber, Matthias J Feige
A fundamental step in membrane protein biogenesis is their integration into the lipid bilayer with a defined orientation of each transmembrane segment. Despite this, it remains unclear how cells detect and handle failures in this process. Here we show that single point mutations in the membrane protein connexin 32 (Cx32), which cause Charcot-Marie-Tooth disease, can cause failures in membrane integration. This leads to Cx32 transport defects and rapid degradation. Our data show that multiple chaperones detect and remedy this aberrant behavior: the ER-membrane complex (EMC) aids in membrane integration of low-hydrophobicity transmembrane segments...
February 8, 2019: Nature Communications
Fang-Shin Nian, Lei-Li Li, Chih-Ya Cheng, Pei-Chun Wu, You-Tai Lin, Cheng-Yung Tang, Bo-Shiun Ren, Chin-Yin Tai, Ming-Ji Fann, Lung-Sen Kao, Chen-Jee Hong, Jin-Wu Tsai
Mutations in RAB18, a member of small G protein, cause Warburg micro syndrome (WARBM), whose clinical features include vision impairment, postnatal microcephaly, and lower limb spasticity. Previously, our Rab18-/- mice exhibited hind limb weakness and spasticity as well as signs of axonal degeneration in the spinal cord and lumbar spinal nerves. However, the cellular and molecular function of RAB18 and its roles in the pathogenesis of WARBM are still not fully understood. Using immunofluorescence staining and expression of Rab18 and organelle markers, we find that Rab18 associates with lysosomes and actively traffics along neurites in cultured neurons...
February 5, 2019: Molecular Neurobiology
Feifei Tao, Gary W Beecham, Adriana P Rebelo, Susan H Blanton, John J Moran, Camila Lopez-Anido, John Svaren, Jasper M Morrow, Lisa Abreu, Devon Rizzo, Callyn A Kirk, Xingyao Wu, Shawna Feely, Camiel Verhamme, Mario A Saporta, David N Herrmann, John W Day, Charlotte J Sumner, Thomas E Lloyd, Jun Li, Sabrina W Yum, Franco Taroni, Frank Baas, Byung-Ok Choi, Davide Pareyson, Steven S Scherer, Mary M Reilly, Michael E Shy, Stephan Züchner
OBJECTIVE: Genetic modifiers in rare disease have long been suspected to contribute to the considerable variance in disease expression, including Charcot-Marie-Tooth disease type 1A (CMT1A). To address this question the Inherited Neuropathy Consortium collected a large standardized sample of such rare CMT1A patients over a period of eight years. CMT1A is caused in most patients by a uniformly sized 1.5Mb duplication event involving the gene PMP22. METHODS: We genotyped DNA samples from 971 CMT1A patients on Illumina beadchips...
January 31, 2019: Annals of Neurology
Li Qin, Canhong Yang, Tianming Lü, Lanying Li, Dandan Zong, Yueying Wu
OBJECTIVE: To investigate the molecular genetic mechanism of Charcot- Marie-Tooth (CMT) disease in a pedigree. METHODS: Genomic DNA was extracted from the peripheral blood of the family members of a pedigree with autosomal dominant CMT disease, and 65 candidate genes of the proband were screened using target exon capture and the next generation sequencing, and the suspicious genes were verified using Sanger sequencing. PolyPhen-2, PROVEAN and SIFT software were used to predict the function of the mutant genes, and PyMOL-1 software was used to simulate the mutant protein structure...
January 30, 2019: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Maxime Jouaud, Stéphane Mathis, Laurence Richard, Anne-Sophie Lia, Laurent Magy, Jean-Michel Vallat
BACKGROUND: Charcot-Marie-Tooth diseases (CMT) are due to abnormalities of many genes, the most frequent being linked to PMP22 (Peripheral Myelin Protein 22). In the past, only spontaneous genetic anomalies occurring in mouse mutants such as Trembler (Tr) mice were available; more recently, several rodent models have been generated for exploration of the pathophysiological mechanisms underlying these neuropathies. METHODS: Based on the personal experience of our team, we describe here the pathological hallmarks of most of these animal models and compare them to the pathological features observed in some CMT patient nerves (CMT types 1A and E; hereditary neuropathy with liability to pressure palsies, HNPP)...
January 21, 2019: Journal of the Neurological Sciences
Andoni Echaniz-Laguna, Philippe Latour
Heterozygous mutations in the inverted formin-2 (INF2) gene provoke focal segmental glomerulosclerosis (FSGS) and intermediate Charcot-Marie-Tooth (CMT) disease with FSGS. Here, we report 4 patients from a three-generation family with a new cryptic splicing INF2 mutation causing autosomal dominant intermediate CMT with minimal glomerular dysfunction. Three males and 1 female with a mean age of 51 years (26-87) presented with a slowly progressive sensorimotor polyneuropathy, pes cavus, and kyphoscoliosis. Mean age at CMT disease onset was 11...
January 24, 2019: Journal of the Peripheral Nervous System: JPNS
Joseph B Nadol, E Tessa Hedley-Whyte, Sami Samir Amr, Jennifer T O Apos Malley, Takefumi Kamakura
Charcot-Marie-Tooth (CMT) syndrome is a clinically and genetically heterogeneous group of neuropathies affecting both peripheral motor and sensory nerves. Progressive sensorineural hearing loss, vestibular abnormalities, and dysfunction of other cranial nerves have been described. This is the second case report of otopathology in a patient with CMT syndrome. Molecular genetic testing of DNA obtained at autopsy revealed a missense variant in the MPZ gene (p.Thr65Ala), pathogenic for an autosomal-dominant form of CMT1B...
January 24, 2019: Audiology & Neuro-otology
Muwoong Kim, Chan Park, Junyang Jung, Seung Geun Yeo
Peripheral nerves, which consist of an axon and a unique glial cell called a Schwann cell, transduce signals from the brain and spinal cord to target organs. Peripheral nerve degeneration leads to distal motor or sensory disorders such as diabetic neuropathy, Charcot-Marie-Tooth disease, and Gullain-Barré syndrome, with symptoms such as dysesthesia, speech impairment, vision change, erectile dysfunction, and urinary incontinence. Schwann cells play an important role in peripheral nerve degeneration. Therefore, revealing the characteristics of Schwann cells will be essential in understanding peripheral neurodegeneration-related diseases for which there is currently no effective treatment...
January 22, 2019: Journal of Molecular Histology
Mansour Haidar, Bob Asselbergh, Elias Adriaenssens, Vicky De Winter, Jean-Pierre Timmermans, Michaela Auer-Grumbach, Manisha Juneja, Vincent Timmerman
HSPB1 (heat shock protein family B [small] member 1) is a ubiquitously expressed molecular chaperone. Most mutations in HSPB1 cause axonal Charcot-Marie-Tooth neuropathy and/or distal hereditary motor neuropathy. In this study we show that mutations in HSPB1 lead to impairment of macroautophagic/autophagic flux. In HSPB1 knockout cells, we demonstrate that HSPB1 is necessary for autophagosome formation, which was rescued upon re-expression of HSPB1. Employing a label-free LC-MS/MS analysis on the various HSPB1 variants (wild type and mutants), we identified autophagy-specific interactors...
January 23, 2019: Autophagy
Paloma González-Sánchez, Jorgina Satrústegui, Francesc Palau, Araceli Del Arco
The pathology of Charcot-Marie-Tooth (CMT), a disease arising from mutations in different genes, has been associated with an impairment of mitochondrial dynamics and axonal biology of mitochondria. Mutations in ganglioside-induced differentiation-associated protein 1 ( GDAP1 ) cause several forms of CMT neuropathy, but the pathogenic mechanisms involved remain unclear. GDAP1 is an outer mitochondrial membrane protein highly expressed in neurons. It has been proposed to play a role in different aspects of mitochondrial physiology, including mitochondrial dynamics, oxidative stress processes, and mitochondrial transport along the axons...
January 18, 2019: International Journal of Molecular Sciences
Arnaud Jacquier, Valérie Risson, Laurent Schaeffer
Neurodegeneration of spinal motoneurons (MNs) is implicated in a large spectrum of neurological disorders including amyotrophic lateral sclerosis, Charcot-Marie-Tooth disease, and spinal muscular atrophy, which are all associated with muscular atrophy. Primary cultures of spinal MNs have been used widely to demonstrate the involvement of specific genes in such diseases and characterize the cellular consequences of their mutations. This protocol models a primary MN culture derived from the seminal work of Henderson and colleagues more than twenty years ago...
January 7, 2019: Journal of Visualized Experiments: JoVE
Nathalie Bernard-Marissal, Gerben van Hameren, Manisha Juneja, Christophe Pellegrino, Lauri Louhivuori, Luca Bartesaghi, Cylia Rochat, Omar El Mansour, Jean-Jacques Médard, Marie Croisier, Catherine Maclachlan, Olivier Poirot, Per Uhlén, Vincent Timmerman, Nicolas Tricaud, Bernard L Schneider, Roman Chrast
Mutations in the MFN2 gene encoding Mitofusin 2 lead to the development of Charcot-Marie-Tooth type 2A (CMT2A), a dominant axonal form of peripheral neuropathy. Mitofusin 2 is localized at both the outer membrane of mitochondria and the endoplasmic reticulum and is particularly enriched at specialized contact regions known as mitochondria-associated membranes (MAM). We observed that expression of MFN2R94Q induces distal axonal degeneration in the absence of overt neuronal death. The presence of mutant protein leads to reduction in endoplasmic reticulum and mitochondria contacts in CMT2A patient-derived fibroblasts, in primary neurons and in vivo, in motoneurons of a mouse model of CMT2A...
January 18, 2019: Proceedings of the National Academy of Sciences of the United States of America
Camila Maria de Oliveira, Helena Fussiger, Pablo Brea Winckler, Jonas Alex Morales Saute
Charcot Marie Tooth disease type 4C (CMT4C) is considered the most frequent autosomal recessive form of CMT worldwide, being described as an early-onset disorder with marked clinical heterogeneity. We report a CMT4C case associated with dropped head syndrome and predominant involvement of proximal muscles. An 11-year-old boy born to consanguineous parents presented with predominantly proximal muscle weakness with facial involvement, associated with dropped head and severe scoliosis. Symptoms started at the age of 3 years-old with frequent falls...
November 29, 2018: Neuromuscular Disorders: NMD
Andrzej Kochański, Dagmara Kabzińska, Weronika Rzepnikowska, Katarzyna Binięda, Artur Kiepura
Hereditary motor and sensory neuropathies (HMSN) also called as Charcot-Marie-Tooth disorders (CMT) are extremely heterogeneous group of disorders of peripheral nervous system. Over 80 genes have been reported in different types of CMT. In all CMT affected patients the main symptoms are slowly progressive wasting of the distal muscles of the lower and upper limbs. To date no efficient therapeutic approach basing upon molecular pathology of CMT has been proposed. This review presents the current state of knowledge concerning clinical, molecular pathogenesis and experimental therapy aspects in CMT disorders...
December 29, 2018: Postepy Biochemii
Zoi Kontogeorgiou, Katerina Nikolaou, Chrisoula Kartanou, Marianthi Breza, Marios Panas, Georgia Karadima, Georgios Koutsis
Charcot-Marie-Tooth disease type 4 C (CMT4C) is an autosomal recessive form of demyelinating peripheral neuropathy caused by mutations in SH3TC2, characterized by early onset, spine deformities and cranial nerve involvement. We screened SH3TC2 in 50 unrelated Greek patients with suspected demyelinating CMT and pedigree compatible with recessive inheritance. All patients had been previously screened for PMP22, GJB1 and MPZ mutations. We found 5 previously identified pathogenic mutations in SH3TC2 distributed among 13 patients in homozygosity or compound heterozygosity (p...
January 17, 2019: Journal of the Peripheral Nervous System: JPNS
Thomas Prukop, Jan Stenzel, Stephanie Wernick, Theresa Kungl, Magdalena Mroczek, Julia Adam, David Ewers, Serguei Nabirotchkin, Klaus-Armin Nave, Rodolphe Hajj, Daniel Cohen, Michael W Sereda
The most common type of Charcot-Marie-Tooth disease is caused by a duplication of PMP22 leading to dysmyelination, axonal loss and progressive muscle weakness (CMT1A). Currently, no approved therapy is available for CMT1A patients. A novel polytherapeutic proof-of-principle approach using PXT3003, a low-dose combination of baclofen, naltrexone and sorbitol, slowed disease progression after long-term dosing in adult Pmp22 transgenic rats, a known animal model of CMT1A. Here, we report an early postnatal, short-term treatment with PXT3003 in CMT1A rats that delays disease onset into adulthood...
2019: PloS One
Delfina Larrea, Marta Pera, Adriano Gonelli, Ruben Quintana Cabrera, H Orhan Akman, Cristina Guardia-Laguarta, Kevin R Velasco, Estela Area-Gomez, Federica Dal Bello, Diego De Stefani, Rita Horvath, Michael E Shy, Eric A Schon, Marta Giacomello
Charcot-Marie-Tooth disease (CMT) type 2A is an axonal form of peripheral neuropathy, due almost exclusively to dominant mutations in the nuclear gene encoding the mitochondrial protein mitofusin-2 (MFN2). However, there is no understanding of the relationship of clinical phenotype to genotype. MFN2 has two functions: it promotes inter-mitochondrial fusion and mediates ER-mitochondrial tethering at mitochondria-associated ER membranes (MAM). MAM regulates a number of key cellular functions, including lipid and calcium homeostasis, and mitochondrial behavior...
January 11, 2019: Human Molecular Genetics
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"