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

Charcot, 1886, Sur une forme particulière d’atrophie musculaire progressive, souvent familiale, debutant par les pieds et les jambes et atteignant plus tard les mains, Rev. Med., 6, 97

Tooth, H.H. (1886). The Peroneal Type of Progressive Muscular Atrophy, H.K. Lewis and Co.

Dyck, P.J., Thomas, P.K., and Lambert, E.H. (1975). Peripheral Neuropathy, W.B. Saunders Company. [1st ed.].

Dyck, P.J., Thomas, P.K., Griffin, J.W., Low, P.A., and Poduslo, J.F. (2005). Peripheral Neuropathy, WB Saunders. [4th ed.].

Harding, 1980, The clinical features of hereditary motor and sensory neuropathy types I and II, Brain, 103, 259, 10.1093/brain/103.2.259

Timmerman, 2013, Overlapping molecular pathological themes link Charcot-Marie-Tooth neuropathies and hereditary spastic paraplegias, Exp. Neurol., 246, 14, 10.1016/j.expneurol.2012.01.010

Reilly, 2011, Charcot-Marie-Tooth disease, J. Peripher. Nerv. Syst., 16, 1, 10.1111/j.1529-8027.2011.00324.x

Saporta, 2013, Inherited peripheral neuropathies, Neurol. Clin., 31, 597, 10.1016/j.ncl.2013.01.009

Bird, 1982, Evidence for linkage of Charcot-Marie-Tooth neuropathy to the Duffy locus on chromosome 1, Am. J. Hum. Genet., 34, 388

Venter, 2001, The sequence of the human genome, Science, 291, 1304, 10.1126/science.1058040

Lander, 2001, Initial sequencing and analysis of the human genome, Nature, 409, 860, 10.1038/35057062

Ng, 2009, Targeted capture and massively parallel sequencing of 12 human exomes, Nature, 461, 272, 10.1038/nature08250

Ng, 2010, Exome sequencing identifies the cause of a mendelian disorder, Nat. Genet., 42, 30, 10.1038/ng.499

Pitceathly, 2012, Genetic dysfunction of MT-ATP6 causes axonal Charcot-Marie-Tooth disease, Neurology, 79, 1145, 10.1212/WNL.0b013e3182698d8d

Suter, 2003, Disease mechanisms in inherited neuropathies, Nat. Rev. Neurosci., 4, 714, 10.1038/nrn1196

Ingenuity Systems. Available online:http://www.ingenuity.com/.

Online Mendelian Inheritance in Man Database (OMIM). Available online:http://ncbi.nlm.nih.gov/omim/.

Inherited Peripheral Neuropathy Mutation Database (IPNMDB). Available online:http://molgen.vib-ua.be/CMTMutations/.

Leiden Open (Source) Variation Database (LOVD). Available online:http://lovd.nl/.

Bird, 1999, Historical perspective of defining Charcot-Marie-Tooth type 1B, Ann. N. Y. Acad. Sci., 883, 6, 10.1111/j.1749-6632.1999.tb08561.x

Vance, 1989, Linkage of Charcot-Marie-Tooth neuropathy type 1a to chromosome 17, Exp. Neurol., 104, 186, 10.1016/S0014-4886(89)80013-5

Raeymaekers, 1989, Localization of the mutation in an extended family with Charcot- Marie-Tooth neuropathy (HMSN I), Am. J. Hum. Genet., 45, 953

Harding, 1990, Linkage of hereditary motor and sensory neuropathy type I to the pericentromeric region of chromosome 17, Am. J. Hum. Genet., 46, 92

Hayasaka, 1993, Charcot-Marie-Tooth neuropathy type 1B is associated with mutations of the myelin P0 gene, Nat. Genet., 5, 31, 10.1038/ng0993-31

Lacroix, 1999, The Roussy-Levy family: From the original description to the gene, Ann. Neurol., 46, 770, 10.1002/1531-8249(199911)46:5<770::AID-ANA13>3.0.CO;2-U

Pareyson, 1999, Heterozygous null mutation in the P0 gene associated with mild Charcot-Marie-Tooth disease, Ann. N. Y. Acad. Sci., 883, 477, 10.1111/j.1749-6632.1999.tb08615.x

Warner, 1996, Clinical phenotypes of different MPZ (P0) mutations may include Charcot-Marie-Tooth 1B, Dejerine-Sottas and congenital hypomyelination, Neuron, 17, 451, 10.1016/S0896-6273(00)80177-4

Schiavon, 1998, Mutations of the same sequence of the myelin P0 gene causing two different phenotypes, Hum. Mutat., 11, S217, 10.1002/humu.1380110170

Timmerman, 1999, The Thr124Met mutation in the peripheral myelin protein zero (MPZ) gene is associated with a clinically distinct Charcot-Marie-Tooth phenotype, Brain, 122, 281, 10.1093/brain/122.2.281

Nelis, 1996, Estimation of the mutation frequencies in Charcot-Marie-Tooth disease type 1 and hereditary neuropathy with liability to pressure palsies: A European collaborative study, Eur. J. Hum. Genet., 4, 25, 10.1159/000472166

Szigeti, 2006, Charcot-Marie-Tooth disease and related hereditary polyneuropathies: Molecular diagnostics determine aspects of medical management, Genet. Med., 8, 86, 10.1097/01.gim.0000200160.29385.73

Patel, 1990, Genetic mapping of autosomal dominant Charcot-Marie-Tooth disease in a large French-Acadian kindred: Identification of new linked markers on chromosome 17, Am. J. Hum. Genet., 46, 801

Timmerman, 1990, Assignment of the Charcot-Marie-Tooth neuropathy type 1 (CMT 1a) gene to 17p11.2-p12, Am. J. Hum. Genet., 47, 680

Raeymaekers, 1991, HMSN Collaborative Research Group Duplication in chromosome 17p11.2 in Charcot-Marie-Tooth neuropathy type 1a (CMT 1a), Neuromuscul. Disord., 1, 93, 10.1016/0960-8966(91)90055-W

Lupski, 1991, DNA duplication associated with Charcot-Marie-Tooth disease type 1A, Cell, 66, 219, 10.1016/0092-8674(91)90613-4

Lupski, J.R., and Stankiewicz, P. (2006). Genomic Disorders: The Genomic Basis of Disease, Humana Press. [1st ed.].

Chance, 1993, DNA deletion associated with hereditary neuropathy with liability to pressure palsies, Cell, 72, 143, 10.1016/0092-8674(93)90058-X

Reiter, 1996, A recombination hotspot responsible for two inherited peripheral neuropathies is located near a mariner transposon-like element, Nat. Genet., 12, 288, 10.1038/ng0396-288

Kennerson, 1997, The Charcot-Marie-Tooth binary repeat contains a gene transcribed from the opposite strand of a partially duplicated region of the COX10 gene, Genomics, 46, 61, 10.1006/geno.1997.5012

Inoue, 2001, The 1.4 Mb CMT1A duplication/HNPP deletion genomic region reveals unique genome architectural features and provides insights into the recent evolution of new genes, Genome Res., 11, 1018, 10.1101/gr.180401

Matsunami, 1992, Peripheral myelin protein-22 gene maps in the duplication in chromosome 17p11.2 associated with Charcot-Marie-Tooth 1A, Nat. Genet., 1, 176, 10.1038/ng0692-176

Patel, 1992, The gene for the peripheral myelin protein PMP-22 is a candidate for Charcot-Marie-Tooth disease type 1A, Nat. Genet., 1, 159, 10.1038/ng0692-159

Timmerman, 1992, The peripheral myelin protein gene PMP-22 is contained within the Charcot-Marie-Tooth disease type 1A duplication, Nat. Genet., 1, 171, 10.1038/ng0692-171

Valentijn, 1992, The peripheral myelin gene PMP-22/GAS-3 is duplicated in Charcot- Marie-Tooth disease type 1A, Nat. Genet., 1, 166, 10.1038/ng0692-166

Lupski, 1992, Gene dosage is a mechanism for Charcot-Marie-Tooth disease type 1A, Nat. Genet., 1, 29, 10.1038/ng0492-29

Palau, 1993, Origin of the de novo duplication in Charcot-Marie-Tooth disease type 1A: Unequal nonsister chromatid exchange during spermatogenesis, Hum. Mol. Genet., 2, 2031, 10.1093/hmg/2.12.2031

Zhang, 2010, Mechanisms for nonrecurrent genomic rearrangements associated with CMT1A or HNPP: Rare CNVs as a cause for missing heritability, Am. J. Hum. Genet., 86, 892, 10.1016/j.ajhg.2010.05.001

Boone, 2011, Genomic medicine and neurological disease, Hum. Genet., 130, 103, 10.1007/s00439-011-1001-1

Stankiewicz, 2010, Structural variation in the human genome and its role in disease, Annu. Rev. Med., 61, 437, 10.1146/annurev-med-100708-204735

Suter, 1992, Trembler mouse carries a point mutation in a myelin gene, Nature, 356, 241, 10.1038/356241a0

Suter, 1992, A leucine-to-proline mutation in the putative first transmembrane domain of the 22-kDa peripheral myelin protein in the trembler-J mouse, Proc. Natl. Acad. Sci. USA, 89, 4382, 10.1073/pnas.89.10.4382

Fledrich, 2012, Murine therapeutic models for Charcot-Marie-Tooth (CMT) disease, Br. Med. Bull., 102, 89, 10.1093/bmb/lds010

Sereda, 2003, Therapeutic administration of progesterone antagonist in a model of Charcot-Marie-Tooth disease (CMT-1A), Nat. Med., 9, 1533, 10.1038/nm957

Passage, 2004, Ascorbic acid treatment corrects the phenotype of a mouse model of Charcot-Marie-Tooth disease, Nat. Med., 10, 396, 10.1038/nm1023

Verhamme, 2009, Oral high dose ascorbic acid treatment for one year in young CMT1A patients: A randomised, double-blind, placebo-controlled phase II trial, BMC Med., 7, 70, 10.1186/1741-7015-7-70

Pareyson, 2008, Clinical and electrophysiological evaluation of 222 patients with Charcot-Marie-Tooth disease type 1A recruited in the CMT-TRIAAL (ascorbic acid therapy for Charcot-Marie-Tooth 1A disease), J. Neurol., 255, 104

Pareyson, 2006, A multicenter, randomized, double-blind, placebo-controlled trial of long-term ascorbic acid treatment in Charcot-Marie-Tooth disease type 1A (CMT-TRIAAL): The study protocol [EudraCT no.: 2006-000032-27], Pharmacol. Res., 54, 436, 10.1016/j.phrs.2006.09.001

Burns, 2009, Ascorbic acid for Charcot-Marie-Tooth disease type 1A in children: A randomised, double-blind, placebo-controlled, safety and efficacy trial, Lancet Neurol., 8, 537, 10.1016/S1474-4422(09)70108-5

Lewis, 2013, High-dosage ascorbic acid treatment in Charcot-Marie-Tooth disease type 1A: Results of a randomized, double-masked, controlled trial, JAMA Neurol., 70, 981, 10.1001/jamaneurol.2013.3178

Micallef, 2009, Effect of ascorbic acid in patients with Charcot-Marie-Tooth disease type 1A: A multicentre, randomised, double-blind, placebo-controlled trial, Lancet Neurol., 8, 1103, 10.1016/S1474-4422(09)70260-1

Saporta, 2011, Charcot-Marie-Tooth disease subtypes and genetic testing strategies, Ann. Neurol., 69, 22, 10.1002/ana.22166

Aretz, S., Rautenstrauss, B., and Timmerman, V. (2010). Clinical utility gene card for: HMSN/HNPP HMSN types 1, 2, 3, 6 (CMT1,2,4, DSN, CHN, GAN, CCFDN, HNA); HNPP. Eur. J. Hum. Genet., 18.

Harding, 1980, Hereditary distal spinal muscular atrophy. A report on 34 cases and a review of the literature, J. Neurol. Sci., 45, 337, 10.1016/0022-510X(80)90177-X

Irobi, 2006, Unravelling the genetics of distal hereditary motor neuronopathies, NeuroMol. Med., 8, 131, 10.1385/NMM:8:1-2:131

Timmerman, 1992, Linkage analysis of distal hereditary motor neuropathy type II (distal HMN II) in a single pedigree, J. Neurol. Sci., 109, 41, 10.1016/0022-510X(92)90091-X

Gyapay, 1994, The 1993–94 Genethon human genetic linkage map [see comments], Nat. Genet., 7, 246, 10.1038/ng0694supp-246

Timmerman, 1996, Distal hereditary motor neuropathy type II (distal HMN II): Mapping of a locus to chromosome 12q24, Hum. Mol. Genet., 5, 1065, 10.1093/hmg/5.7.1065

Irobi, 2000, A clone contig of 12q24.3 encompassing the distal hereditary motor neuropathy type II gene, Genomics, 65, 34, 10.1006/geno.2000.6149

Irobi, 2004, Hot-spot residue in small heat-shock protein 22 causes distal motor neuropathy, Nat. Genet., 36, 597, 10.1038/ng1328

Ismailov, 2001, A new locus for autosomal dominant Charcot-Marie-Tooth disease type 2 (CMT2F) maps to chromosome 7q11-q21, Eur. J. Hum. Genet., 9, 646, 10.1038/sj.ejhg.5200686

Evgrafov, 2004, Mutant small heat-shock protein 27 causes axonal Charcot-Marie-Tooth disease and distal hereditary motor neuropathy, Nat. Genet., 36, 602, 10.1038/ng1354

Holmgren, A., Bouhy, D., and Timmerman, V. (2012). Molecular Biology of small HSPs associated with Peripheral Neuropathies. eLS.

Krishnan, 2011, HDAC6 inhibitors reverse axonal loss in a mouse model of mutant HSPB1-induced Charcot-Marie-Tooth disease, Nat. Med., 17, 968, 10.1038/nm.2396

Saito, 1997, Linkage mapping of the gene for Charcot-Marie-Tooth disease type 2 to chromosome 1p (CMT2A) and the clinical features of CMT2A, Neurology, 49, 1630, 10.1212/WNL.49.6.1630

Zhao, 2001, Charcot-Marie-Tooth disease type 2A caused by mutation in a microtubule motor KIF1Bbeta, Cell, 105, 587, 10.1016/S0092-8674(01)00363-4

Zuchner, 2004, Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A, Nat. Genet., 36, 449, 10.1038/ng1341

Verhoeven, 2006, Mitofusin 2 mutation distribution and genotype/phenotype correlation in Charcot-Marie-Tooth type 2, Brain, 129, 2093, 10.1093/brain/awl126

Lv, 2013, Mitofusin 2 gene mutation causing early-onset CMT2A with different progressive courses, Clin. Neuropathol., 32, 16, 10.5414/NP300464

Chung, 2006, Early onset severe and late-onset mild Charcot-Marie-Tooth disease with mitofusin 2 (MFN2) mutations, Brain, 129, 2103, 10.1093/brain/awl174

Feely, 2011, MFN2 mutations cause severe phenotypes in most patients with CMT2A, Neurology, 76, 1690, 10.1212/WNL.0b013e31821a441e

Jordanova, 2006, Axonal neuropathy with optic atrophy (HMSN VI) is caused by mutations in mitofusin 2, Ann. Neurol., 59, 276, 10.1002/ana.20797

Zhu, 2005, Charcot-Marie-Tooth with pyramidal signs is genetically heterogeneous: Families with and without MFN2 mutations, Neurology, 65, 496, 10.1212/01.wnl.0000171345.62270.29

McCorquodale, 2011, Mutation screening of mitofusin 2 in Charcot-Marie-Tooth disease type 2, J. Neurol., 258, 1234, 10.1007/s00415-011-5910-7

Weger, 2011, Fibulin-5 mutations link inherited neuropathies, age-related macular degeneration and hyperelastic skin, Brain, 134, 1839, 10.1093/brain/awr076

Zimon, 2012, Loss-of-function mutations in HINT1 cause axonal neuropathy with neuromyotonia, Nat. Genet., 44, 1080, 10.1038/ng.2406

Azzedine, 2012, Molecular genetics of charcot-marie-tooth disease: From genes to genomes, Mol. Syndromol., 3, 204, 10.1159/000343487

Rossor, 2013, Clinical implications of genetic advances in Charcot-Marie-Tooth disease, Nat. Rev. Neurol., 9, 562, 10.1038/nrneurol.2013.179

Montenegro, 2011, Exome sequencing allows for rapid gene identification in a Charcot-Marie-Tooth family, Ann. Neurol., 69, 464, 10.1002/ana.22235

Gonzales, 2013, Exome sequencing identifies a significant variant in methionyl-tRNA synthetase (MARS) in a family with late-onset CMT2, J. Neurol. Neurosurg. Psychiatry, 84, 1247, 10.1136/jnnp-2013-305049

Peeters, 2013, Molecular defects in the motor adaptor BICD2 Cause proximal spinal muscular atrophy with autosomal-dominant inheritance, Am. J. Hum. Genet., 92, 955, 10.1016/j.ajhg.2013.04.013

Neveling, 2013, Mutations in BICD2, which encodes a golgin and important motor adaptor, cause congenital autosomal-dominant spinal muscular atrophy, Am. J. Hum. Genet., 92, 946, 10.1016/j.ajhg.2013.04.011

Oates, 2013, Mutations in BICD2 cause dominant congenital spinal muscular atrophy and hereditary spastic paraplegia, Am. J. Hum. Genet., 92, 965, 10.1016/j.ajhg.2013.04.018

Kennerson, 2013, A new locus for X-linked dominant Charcot-Marie-Tooth disease (CMTX6) is caused by mutations in the pyruvate dehydrogenase kinase isoenzyme 3 (PDK3) gene, Hum. Mol. Genet., 22, 1404, 10.1093/hmg/dds557

Leipold, 2013, A de novo gain-of-function mutation in SCN11A causes loss of pain perception, Nat. Genet., 45, 1399, 10.1038/ng.2767

Barwick, 2012, Defective presynaptic choline transport underlies hereditary motor neuropathy, Am. J. Hum. Genet., 91, 1103, 10.1016/j.ajhg.2012.09.019

Tischfield, 2010, Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance, Cell, 140, 74, 10.1016/j.cell.2009.12.011

Lupski, 2010, Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy, N. Engl. J. Med., 362, 1181, 10.1056/NEJMoa0908094

2010, Peripheral neuropathies: Whole genome sequencing identifies causal variants in CMT, Nat. Rev. Neurol., 6, 424, 10.1038/nrneurol.2010.108

Senderek, 2003, Mutations in a gene encoding a novel SH3/TPR domain protein cause autosomal recessive Charcot-Marie-Tooth type 4C neuropathy, Am. J. Hum. Genet., 73, 1106, 10.1086/379525

Gonzalez, 2013, GEnomes Management Application (GEM.app): A new software tool for large-scale collaborative genome analysis, Hum. Mutat., 34, 842, 10.1002/humu.22305

Genome Variant Database for Human Diseases. Available online:http://www.genomics.med.miami.edu/.

Human Gene Mutation Database. Available online:http://www.biobase-international.com/product/hgmd/.

Inherited Neuropathy Consortium. Available online:http://rarediseasesnetwork.epi.usf.edu/INC/.

Niemann, 2006, Pathornechanisms of mutant proteins in Charcot-Marie-Tooth disease, NeuroMol. Med., 8, 217, 10.1385/NMM:8:1-2:217

Bouhy, 2013, Animal models and therapeutic prospects for Charcot-Marie-Tooth disease, Ann. Neurol., 74, 391, 10.1002/ana.23987