Charcot-Marie-Tooth disease and pathways to molecular based therapies.
The discovery in 1991 that chromosome 17p12 duplication is associated with Charcot-Marie-Tooth (CMT) disease marked the beginning of an era of molecular insight into this disorder, which encompasses the peripheral motor and sensory neuropathies. A mere two decades later, over 40 subtypes of CMT have been molecularly defined and many have been extensively studied in vitro and in animal models, providing the framework for a more comprehensive understanding of the biological pathways dictating myelination, axonal dynamics, and axon-glia interactions. The advent of next-generation sequencing technologies offers opportunities in both research and clinical settings for gene discovery, further molecular understanding and diagnosis, and calls for modifications of the existing algorithms guiding genetic testing. Although treatment is mainly supportive at this time, advances in this field are anticipated as the molecular basis of CMT is unraveled.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
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Harel
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Lupski
D000818:Animals; D002607:Charcot-Marie-Tooth Disease / Q000145:classification / Q000175:diagnosis / Q000473:pathology / Q000628:therapy*; D005820:Genetic Testing; D006801:Humans; D025202:Molecular Diagnostic Techniques; D058990:Molecular Targeted Therapy; D010641:Phenotype
CMT1A duplication; Charcot-Marie-Tooth; Schwann cell dynamics; axonal dysfunction; symmetric distal polyneuropathy; whole-exome sequencing