Genetics of Charcot-Marie-Tooth (CMT) disease within the frame of the human genome project success

Vincent Timmerman, Alleene V. Strickland, Stephan L Zuchner

Research output: Contribution to journalArticle

113 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)13-32
Number of pages20
JournalGenes
Volume5
Issue number1
DOIs
StatePublished - Mar 1 2014

Fingerprint

Human Genome Project
Charcot-Marie-Tooth Disease
Tooth
Genetic Association Studies
Mutation
Genome
Inheritance Patterns
Nerve Degeneration
Genetic Research
Gene Regulatory Networks
Medical Genetics
Peripheral Nervous System Diseases
Peripheral Nerves
Genes
History
Technology
Costs and Cost Analysis
DNA

Keywords

  • Charcot-marie-tooth
  • Gene discoveries
  • Genomic disorders
  • Next generation sequencing
  • Peripheral neuropathy

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Genetics of Charcot-Marie-Tooth (CMT) disease within the frame of the human genome project success. / Timmerman, Vincent; Strickland, Alleene V.; Zuchner, Stephan L.

In: Genes, Vol. 5, No. 1, 01.03.2014, p. 13-32.

Research output: Contribution to journalArticle

Timmerman, Vincent ; Strickland, Alleene V. ; Zuchner, Stephan L. / Genetics of Charcot-Marie-Tooth (CMT) disease within the frame of the human genome project success. In: Genes. 2014 ; Vol. 5, No. 1. pp. 13-32.
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