Genes 2014, 5(1), 13-32; doi:10.3390/genes5010013
Review

Genetics of Charcot-Marie-Tooth (CMT) Disease within the Frame of the Human Genome Project Success

1,2,* email, 3email and 3,* email
Received: 20 November 2013; in revised form: 8 January 2014 / Accepted: 10 January 2014 / Published: 22 January 2014
(This article belongs to the Special Issue Grand Celebration: 10th Anniversary of the Human Genome Project)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: Charcot-Marie-Tooth (CMT) neuropathies comprise a group of monogenic disorders affecting the peripheral nervous system. CMT is characterized by a clinically and genetically heterogeneous group of neuropathies, involving all types of Mendelian inheritance patterns. Over 1,000 different mutations have been discovered in 80 disease-associated genes. Genetic research of CMT has pioneered the discovery of genomic disorders and aided in understanding the effects of copy number variation and the mechanisms of genomic rearrangements. CMT genetic study also unraveled common pathomechanisms for peripheral nerve degeneration, elucidated gene networks, and initiated the development of therapeutic approaches. The reference genome, which became available thanks to the Human Genome Project, and the development of next generation sequencing tools, considerably accelerated gene and mutation discoveries. In fact, the first clinical whole genome sequence was reported in a patient with CMT. Here we review the history of CMT gene discoveries, starting with technologies from the early days in human genetics through the high-throughput application of modern DNA analyses. We highlight the most relevant examples of CMT genes and mutation mechanisms, some of which provide promising treatment strategies. Finally, we propose future initiatives to accelerate diagnosis of CMT patients through new ways of sharing large datasets and genetic variants, and at ever diminishing costs.
Keywords: Charcot-Marie-Tooth; peripheral neuropathy; genomic disorders; gene discoveries; next generation sequencing
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MDPI and ACS Style

Timmerman, V.; Strickland, A.V.; Züchner, S. Genetics of Charcot-Marie-Tooth (CMT) Disease within the Frame of the Human Genome Project Success. Genes 2014, 5, 13-32.

AMA Style

Timmerman V, Strickland AV, Züchner S. Genetics of Charcot-Marie-Tooth (CMT) Disease within the Frame of the Human Genome Project Success. Genes. 2014; 5(1):13-32.

Chicago/Turabian Style

Timmerman, Vincent; Strickland, Alleene V.; Züchner, Stephan. 2014. "Genetics of Charcot-Marie-Tooth (CMT) Disease within the Frame of the Human Genome Project Success." Genes 5, no. 1: 13-32.

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