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

摘要: Charcot-Marie-Tooth (CMT) neuropathies comprise a group of monogenic disorders affecting the peripheral nervous system. CMT is characterized by clinically and genetically heterogeneous neuropathies, involving all types Mendelian inheritance patterns. Over 1,000 different mutations have been discovered in 80 disease-associated genes. Genetic research has pioneered discovery genomic aided understanding effects copy number variation mechanisms rearrangements. genetic study also unraveled common pathomechanisms for nerve degeneration, elucidated gene networks, initiated development therapeutic approaches. The reference genome, which became available thanks to Human Genome Project, next generation sequencing tools, considerably accelerated mutation discoveries. In fact, first clinical whole genome sequence was reported patient with CMT. Here we review history discoveries, starting technologies from early days human genetics through high-throughput application modern DNA analyses. We highlight most relevant examples genes mechanisms, some provide promising treatment strategies. Finally, propose future initiatives accelerate diagnosis patients new ways sharing large datasets variants, at ever diminishing costs.