Charcot-Marie-Tooth Project

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The real promise of genomics will not be realized until individual patients enjoy improved medical outcomes due to the understanding that genome sequencing can bring to their treatment. At the BCM-HGSC we are working together with Jim Lupski and other BCM collaborators to demonstrate that this promise can be a reality with current DNA sequencing technology.

Sequencing to Solve Genetic Disease

Our current focus is on Charcot-Marie-Tooth (CMT) disease, an inherited peripheral neuropathy with both demyelinating (CMT type 1, CMT1) and axonal (CMT2) forms, distinguished by electrophysiologic and/or neuropathologic studies. CMT has been used as a model disease to describe genetic heterogeneity, to posit the relation of hereditary pattern to clinical severity, and to investigate the relative importance of principal and modifying genes in determining human diseases. It’s role as a model for genetic disease makes it the ideal starting point for these early studies in medical genomics.

Currently we have sequenced the whole genome of one CMT patient, and are progressing to sequence additional samples within that patient’s family, as well as identifying other patients that may benefit from these early experiments.

Additional Resources

Learn more about Charcot-Marie-Tooth disease

Related Publications

Pehlivan D, Beck CR, Okamoto Y, Harel T, Akdemir ZHC, Jhangiani SN, et al. The role of combined SNV and CNV burden in patients with distal symmetric polyneuropathy. Genet Med. 2016 ;18(5):443-51.

Gonzaga-Jauregui C, Harel T, Gambin T, Kousi M, Griffin LB, Francescatto L, et al. Exome Sequence Analysis Suggests that Genetic Burden Contributes to Phenotypic Variability and Complex Neuropathy. Cell Rep. 2015 ;12(7):1169-83.

Pehlivan D, Akdemir ZCoban, Karaca E, Bayram Y, Jhangiani S, Yildiz EPembegul, et al. Exome sequencing reveals homozygous TRIM2 mutation in a patient with early onset CMT and bilateral vocal cord paralysis. Hum Genet. 2015 ;134(6):671-3.

Liu P, Gelowani V, Zhang F, Drory VE, Ben-Shachar S, Roney E, et al. Mechanism, prevalence, and more severe neuropathy phenotype of the Charcot-Marie-Tooth type 1A triplication. Am J Hum Genet. 2014 ;94(3):462-9.

Okamoto Y, Goksungur MTuba, Pehlivan D, Beck CR, Gonzaga-Jauregui C, Muzny DM, et al. Exonic duplication CNV of NDRG1 associated with autosomal-recessive HMSN-Lom/CMT4D. Genet Med. 2014 ;16(5):386-94.

Lupski JR, Reid JG, Gonzaga-Jauregui C, Deiros DRio, C Y Chen D, Nazareth L, et al. Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy. N Engl J Med. 2010 ;362(13):1181-91.

Reiter LT, Murakami T, Koeuth T, Gibbs RA, Lupski JR. The human COX10 gene is disrupted during homologous recombination between the 24 kb proximal and distal CMT1A-REPs. Hum Mol Genet. 1997 ;6(9):1595-603.

Reiter LT, Murakami T, Koeuth T, Pentao L, Muzny DM, Gibbs RA, et al. A recombination hotspot responsible for two inherited peripheral neuropathies is located near a mariner transposon-like element. Nat Genet. 1996 ;12(3):288-97.