Journal ArticleDOI
Clinical implications of genetic advances in Charcot–Marie–Tooth disease
TLDR
This Review discusses how NGS is being employed in the diagnostic evaluation of patients with CMT and how the genetic advances in CMT are influencing clinical practice, and explores how genetic advances have broadened the phenotype of C MT and related disorders.Abstract:
Charcot-Marie-Tooth disease (CMT) refers to a group of inherited neuropathies with a broad range of phenotypes, inheritance patterns and causative genes The number of disease genes identified in CMT has expanded rapidly over the past few decades, such that more than 60 CMT-associated genes have now been discovered This rise in genetic discovery can be attributed to the development of next-generation sequencing (NGS) technology, which allows the entire exome or genome to be sequenced in a matter of days In this Review, we discuss how NGS is being employed in the diagnostic evaluation of patients with CMT and how the genetic advances in CMT are influencing clinical practice In particular, we explore how genetic advances have broadened the phenotype of CMT and related disorders and how NGS allows a large number of CMT genes to be screened simultaneously early in the evaluation of an unexplained neuropathy Finally, we discuss the different methods of NGS that can be used in CMT and related disorders, and propose a simple diagnostic algorithm in which clinical assessment and neurophysiology are used to guide the application of phenotype specific 'panels'read more
Citations
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Journal ArticleDOI
Schwann Cell Myelination
TL;DR: Current understanding of the development, molecular organization, and function of the myelinating Schwann cells is reviewed and recent findings into the extrinsic signals that drive Schwann cell myelination, their cognate receptors, and the downstream intracellular signaling pathways they activate are described.
Journal ArticleDOI
Regulation of the Epigenome by Vitamin C
TL;DR: An interdisciplinary research field is suggested that can be termed redox genomics to study dynamic redox processes in health and diseases to bridge the gap between redox biology and genomics.
Journal ArticleDOI
CMT subtypes and disease burden in patients enrolled in the Inherited Neuropathies Consortium natural history study: a cross-sectional analysis
Vera Fridman,Brian N. Bundy,Mary M. Reilly,Davide Pareyson,Chelsea Bacon,Joshua Burns,John W. Day,Shawna M. E. Feely,Richard S. Finkel,Tiffany Grider,Callyn A. Kirk,David N. Herrmann,Matilde Laura,Jun Li,Thomas E. Lloyd,Charlotte J. Sumner,Francesco Muntoni,Giuseppe Piscosquito,Sindhu Ramchandren,Sindhu Ramchandren,R Shy,Carly E. Siskind,Sabrina W. Yum,Isabella Moroni,Emanuela Pagliano,Stephan Züchner,Steven S. Scherer,Michael E. Shy,Michael E. Shy +28 more
TL;DR: This study confirms that it is possible to assess patients in a uniform way between international centres, which is critical for the planned natural history study and future clinical trials, and confirms that large numbers of patients with a representative variety of CMT subtypes have been enrolled.
Journal ArticleDOI
Genetics of Charcot-Marie-Tooth (CMT) Disease within the Frame of the Human Genome Project Success
TL;DR: The history of CMT gene discoveries is reviewed, starting with technologies from the early days in human genetics through the high-throughput application of modern DNA analyses, and some of which provide promising treatment strategies are highlighted.
Journal ArticleDOI
New insights on schwann cell development
TL;DR: Both seminal discoveries and recent advances in understanding of the molecular mechanisms that drive Schwann cell development and myelination are discussed, with a focus on cell–cell and cell–matrix signaling events.
References
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Journal ArticleDOI
Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification
Jan P. Schouten,Cathal J. McElgunn,Raymond Waaijer,Danny A. Zwijnenburg,Filip Diepvens,Gerard Pals +5 more
TL;DR: A new method for relative quantification of 40 different DNA sequences in an easy to perform reaction requiring only 20 ng of human DNA is described.
Journal ArticleDOI
Whole-Genome Sequencing in a Patient with Charcot–Marie–Tooth Neuropathy
James R. Lupski,Jeffrey G. Reid,Claudia Gonzaga-Jauregui,David Rio Deiros,David C.Y. Chen,Lynne V. Nazareth,Matthew N. Bainbridge,Huyen Dinh,Chyn Jing,David A. Wheeler,Amy L. McGuire,Feng Zhang,Pawel Stankiewicz,John J. Halperin,Chengyong Yang,Curtis Gehman,Danwei Guo,Rola K. Irikat,Warren Tom,Nick J. Fantin,Donna M. Muzny,Richard A. Gibbs +21 more
TL;DR: As shown in this study of a family with Charcot-Marie-Tooth disease, whole-genome sequencing can identify clinically relevant variants and provide diagnostic information to inform the care of patients.
Journal ArticleDOI
Duplication in chromosome 17p11.2 in Charcot-Marie-Tooth neuropathy type 1a (CMT 1a). The HMSN Collaborative Research Group.
P Raeymaekers,Vincent Timmerman,Eva Nelis,P. De Jonghe,Jessica E. Hoogendijk,Frank Baas,David F. Barker,J.J. Martin,M. de Visser,P.A. Bolhuis +9 more
TL;DR: It is proposed that the duplication in 17p11.2 itself is the disease causing mutation in all the HMSN I families analyzed, and different allelic combinations were found segregating with the duplicates in different families linkage disequilibrium was not a significant factor.
Journal ArticleDOI
HDAC6 inhibitors reverse axonal loss in a mouse model of mutant HSPB1–induced Charcot-Marie-Tooth disease
Constantin d’Ydewalle,J. Krishnan,Driss Chiheb,Philip Van Damme,Joy Irobi,Alan P. Kozikowski,Pieter Vanden Berghe,Vincent Timmerman,Wim Robberecht,Ludo Van Den Bosch +9 more
TL;DR: An increase of α-tubulin acetylation induced by pharmacological inhibition of histone deacetylase 6 (HDAC6) corrected the axonal transport defects caused by HSPB1 mutations and rescued the CMT phenotype of symptomatic mutant H SPB1 mice.
Journal ArticleDOI
Charcot-Marie-Tooth Disease Subtypes and Genetic Testing Strategies
Anita S. D. Saporta,Stephanie L. Sottile,Lindsey J. Miller,Shawna M. E. Feely,Carly E. Siskind,Michael E. Shy +5 more
TL;DR: A large number of the genes involved inarcot‐Marie‐Tooth disease are unknown, but it is unclear how these genes contribute to the disease or how they are passed on through the immune system.
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