Genetic Workup for Charcot–Marie–Tooth Neuropathy: A Retrospective Single-Site Experience Covering 15 Years
Abstract
:1. Introduction
2. Materials and Methods
3. Results
3.1. Genetically Confirmed Patients
3.2. Patients without Genetic Confirmation
3.3. Genotype–Phenotype Correlation: A New CMT Phenotype
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
- Barreto, L.C.L.S.; Oliveira, F.S.; Nunes, P.S.; De França Costa, I.M.P.; Garcez, C.A.; Goes, G.M.; Neves, E.L.A.; De Souza Siqueira Quintans, J.; De Souza Araújo, A.A. Epidemiologic Study of Charcot-Marie-Tooth Disease: A Systematic Review. Neuroepidemiology 2016, 46, 157–165. [Google Scholar] [CrossRef] [PubMed]
- Rossor, A.M.; Tomaselli, P.J.; Reilly, M.M. Recent advances in the genetic neuropathies. Curr. Opin. Neurol. 2016, 29, 537–548. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Berciano, J.; García, A.; Gallardo, E.; Peeters, K.; Pelayo-Negro, A.L.; Álvarez-Paradelo, S.; Gazulla, J.; Martínez-Tames, M.; Infante, J.; Jordanova, A. Intermediate Charcot–Marie–Tooth disease: An electrophysiological reappraisal and systematic review. J. Neurol. 2017, 264, 1655–1677. [Google Scholar] [CrossRef] [PubMed]
- Rossor, A.M.; Polke, J.M.; Houlden, H.; Reilly, M.M. Clinical implications of genetic advances in charcot-marie-tooth disease. Nat. Rev. Neurol. 2013, 9, 562–571. [Google Scholar] [CrossRef]
- Gess, B.; Schirmacher, A.; Boentert, M.; Young, P. Charcot-Marie-Tooth disease: Frequency of genetic subtypes in a German neuromuscular center population. Neuromuscul. Disord. 2013, 23, 647–651. [Google Scholar] [CrossRef]
- McCorquodale, D.; Pucillo, E.M.; Johnson, N.E. Management of Charcot–Marie–Tooth disease: Improving long-term care with a multidisciplinary approach. J. Multidiscip. Healthc. 2016, 19, 7–19. [Google Scholar] [CrossRef] [Green Version]
- Nicholson, G.; Myers, S. Intermediate forms of charcot-marie-tooth neuropathy: A review. NeuroMolecular Med. 2006, 8, 123–130. [Google Scholar] [CrossRef]
- Shy, M.E.; Blake, J.; Krajewski, K.; Fuerst, D.R.; Laura, M.; Hahn, A.F.; Li, J.; Lewis, R.A.; Reilly, M. Reliability and validity of the CMT neuropathy score as a measure of disability. Neurology. 2005, 12, 1209–1214. [Google Scholar] [CrossRef]
- Murphy, S.M.; Herrmann, D.N.; McDermott, M.P.; Scherer, S.S.; Shy, M.E.; Reilly, M.M.; Pareyson, D. Reliability of the CMT neuropathy score (second version) in Charcot-Marie-Tooth disease. J. Peripher. Nerv. Syst. 2011, 16, 191–198. [Google Scholar] [CrossRef] [Green Version]
- Jani-Acsadi, A.; Krajewski, K.; Shy, M.E. Charcot-Marie-Tooth neuropathies: Diagnosis and management. Semin. Neurol. 2008, 28, 185–194. [Google Scholar] [CrossRef] [Green Version]
- Wang, K.; Li, M.; Hakonarson, H. ANNOVAR: Functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 2010, 38, e164. [Google Scholar] [CrossRef] [PubMed]
- Grandis, M.; Shy, M.E. Current therapy for Charcot-Marie-Tooth disease. Curr. Treat. Options Neurol. 2005, 7, 23–31. [Google Scholar] [CrossRef] [PubMed]
- Videler, A.J.; Beelen, A.; Van Schaik, I.N.; De Visser, M.; Nollet, F. Limited upper limb functioning has impact on restrictions in participation and autonomy of patients with hereditary motor and sensory neuropathy 1A. J. Rehabil. Med. 2009, 41, 746–750. [Google Scholar] [CrossRef] [Green Version]
- Mandich, P.; Grandis, M.; Geroldi, A.; Acquaviva, M.; Varese, A.; Gulli, R.; Ciotti, P.; Bellone, E. Gap junction beta 1 (GJB1) gene mutations in Italian patients with X-linked Charcot-Marie-Tooth disease. J. Hum. Genet. 2008, 53, 529–533. [Google Scholar] [CrossRef] [Green Version]
- Pareyson, D.; Marchesi, C. Diagnosis, natural history, and management of Charcot-Marie-Tooth disease. Lancet Neurol. 2009, 8, 654–667. [Google Scholar] [CrossRef]
- Choi, B.O.; Koo, S.K.; Park, M.H.; Rhee, H.; Yang, S.J.; Choi, K.G.; Jung, S.C.; Kim, H.S.; Hyun, Y.S.; Nakhro, K.; et al. Exome sequencing is an efficient tool for genetic screening of Charcot-Marie-Tooth Disease. Hum. Mutat. 2012, 33, 1610–1615. [Google Scholar] [CrossRef] [PubMed]
- Høyer, H.; Braathen, G.J.; Busk, Ø.L.; Holla, Ø.L.; Svendsen, M.; Hilmarsen, H.T.; Strand, L.; Skjelbred, C.F.; Russell, M.B. Genetic diagnosis of Charcot-Marie-Tooth disease in a population by next-generation sequencing. Biomed. Res. Int. 2014, 2014, 210401. [Google Scholar] [CrossRef] [Green Version]
- Antoniadi, T.; Buxton, C.; Dennis, G.; Forrester, N.; Smith, D.; Lunt, P.; Burton-Jones, S. Application of targeted multi-gene panel testing for the diagnosis of inherited peripheral neuropathy provides a high diagnostic yield with unexpected phenotype-genotype variability. BMC Med. Genet. 2015, 16, 84. [Google Scholar] [CrossRef] [Green Version]
- Drew, A.P.; Zhu, D.; Kidambi, A.; Ly, C.; Tey, S.; Brewer, M.H.; Ahmad-Annuar, A.; Nicholson, G.A.; Kennerson, M.L. Improved inherited peripheral neuropathy genetic diagnosis by whole-exome sequencing. Mol. Genet. Genom. Med. 2015, 3, 143–154. [Google Scholar] [CrossRef]
- Lupo, V.; García-García, F.; Sancho, P.; Tello, C.; García-Romero, M.; Villarreal, L.; Alberti, A.; Sivera, R.; Dopazo, J.; Pascual-Pascual, S.I.; et al. Assessment of Targeted Next-Generation Sequencing as a Tool for the Diagnosis of Charcot-Marie-Tooth Disease and Hereditary Motor Neuropathy. J. Mol. Diagn. 2016, 18, 225–234. [Google Scholar] [CrossRef]
- Nam, S.H.; Hong, Y.B.; Hyun, Y.S.; Nam, D.E.; Kwak, G.; Hwang, S.H.; Choi, B.O.; Chung, K.W. Identification of genetic causes of inherited peripheral neuropathies by targeted gene panel sequencing. Mol. Cells 2016, 39, 382–388. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Laššuthová, P.; Šafka Brožková, D.; Krůtová, M.; Neupauerová, J.; Haberlová, J.; Mazanec, R.; Dřímal, P.; Seeman, P. Improving diagnosis of inherited peripheral neuropathies through gene panel analysis. Orphanet J. Rare Dis. 2016, 11, 118. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dohrn, M.F.; Glöckle, N.; Mulahasanovic, L.; Heller, C.; Mohr, J.; Bauer, C.; Riesch, E.; Becker, A.; Battke, F.; Hörtnagel, K.; et al. Frequent genes in rare diseases: Panel-based next generation sequencing to disclose causal mutations in hereditary neuropathies. J. Neurochem. 2017, 143, 507–522. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bansagi, B.; Griffin, H.; Whittaker, R.G.; Antoniadi, T.; Evangelista, T.; Miller, J.; Greenslade, M.; Forester, N.; Duff, J.; Bradshaw, A.; et al. Genetic heterogeneity of motor neuropathies. Neurology 2017, 88, 1226–1234. [Google Scholar] [CrossRef] [Green Version]
- He, J.; Guo, L.; Xu, G.; Xu, L.; Lin, S.; Chen, W.; Wang, N. Clinical and genetic investigation in Chinese patients with demyelinating Charcot-Marie-Tooth disease. J. Peripher. Nerv. Syst. 2018, 23, 216–226. [Google Scholar] [CrossRef]
- Bacquet, J.; Stojkovic, T.; Boyer, A.; Martini, N.; Audic, F.; Chabrol, B.; Salort-Campana, E.; Delmont, E.; Desvignes, J.P.; Verschueren, A.; et al. Molecular diagnosis of inherited peripheral neuropathies by targeted next-generation sequencing: Molecular spectrum delineation. BMJ Open 2018, 8, e021632. [Google Scholar] [CrossRef] [Green Version]
- Hartley, T.; Wagner, J.D.; Warman-Chardon, J.; Tétreault, M.; Brady, L.; Baker, S.; Tarnopolsky, M.; Bourque, P.R.; Parboosingh, J.S.; Smith, C.; et al. Whole-exome sequencing is a valuable diagnostic tool for inherited peripheral neuropathies: Outcomes from a cohort of 50 families. Clin. Genet. 2018, 93, 301–309. [Google Scholar] [CrossRef]
- Vaeth, S.; Christensen, R.; Dunø, M.; Lildballe, D.L.; Thorsen, K.; Vissing, J.; Svenstrup, K.; Hertz, J.M.; Andersen, H.; Jensen, U.B. Genetic analysis of Charcot-Marie-Tooth disease in Denmark and the implementation of a next generation sequencing platform. Eur. J. Med. Genet. 2019, 62, 1–8. [Google Scholar] [CrossRef] [Green Version]
- Yoshimura, A.; Yuan, J.H.; Hashiguchi, A.; Ando, M.; Higuchi, Y.; Nakamura, T.; Okamoto, Y.; Nakagawa, M.; Takashima, H. Genetic profile and onset features of 1005 patients with Charcot-Marie-Tooth disease in Japan. J. Neurol. Neurosurg. Psychiatry 2019, 90, 195–202. [Google Scholar] [CrossRef] [Green Version]
- Lee, D.C.; Dankwa, L.; Edmundson, C.; Cornblath, D.R.; Scherer, S.S. Yield of next-generation neuropathy gene panels in axonal neuropathies. J. Peripher. Nerv. Syst. 2019, 24, 324–329. [Google Scholar] [CrossRef]
- Liu, X.; Duan, X.; Zhang, Y.; Sun, A.; Fan, D. Molecular analysis and clinical diversity of distal hereditary motor neuropathy. Eur. J. Neurol. 2020, 27, 1319–1326. [Google Scholar] [CrossRef] [PubMed]
- Cortese, A.; Wilcox, J.E.; Polke, J.M.; Poh, R.; Skorupinska, M.; Rossor, A.M.; Laura, M.; Tomaselli, P.J.; Houlden, H.; Shy, M.E.; et al. Targeted next-generation sequencing panels in the diagnosis of Charcot-Marie-Tooth disease. Neurology 2020, 94, e51–e61. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lin, S.; Xu, L.Q.; Xu, G.R.; Guo, L.L.; Lin, B.J.; Chen, W.J.; Wang, N.; Lin, Y.; He, J. Whole exome sequencing reveals a broader variant spectrum of Charcot-Marie-Tooth disease type 2. Neurogenetics 2020, 21, 79–86. [Google Scholar] [CrossRef] [PubMed]
- Ferese, R.; Campopiano, R.; Scala, S.; D’Alessio, C.; Storto, M.; Buttari, F.; Centonze, D.; Logroscino, G.; Zecca, C.; Zampatti, S.; et al. Cohort Analysis of 67 Charcot-Marie-Tooth Italian Patients: Identification of New Mutations and Broadening of Phenotype Expression Produced by Rare Variants. Front. Genet. 2021, 12, 682050. [Google Scholar] [CrossRef]
- Volodarsky, M.; Kerkhof, J.; Stuart, A.; Levy, M.; Brady, L.I.; Tarnopolsky, M.; Lin, H.; Ainsworth, P.; Sadikovic, B. Comprehensive genetic sequence and copy number analysis for Charcot-Marie-Tooth disease in a Canadian cohort of 2517 patients. J. Med. Genet. 2021, 58, 284–288. [Google Scholar] [CrossRef]
- Felice, K.J.; Whitaker, C.H.; Khorasanizadeh, S. Diagnostic yield of advanced genetic testing in patients with hereditary neuropathies: A retrospective single-site study. Muscle Nerve 2021, 64, 454–461. [Google Scholar] [CrossRef]
- Saporta, A.S.D.; Sottile, S.L.; Miller, L.J.; Feely, S.M.E.; Siskind, C.E.; Shy, M.E. Charcot-marie-tooth disease subtypes and genetic testing strategies. Ann. Neurol. 2011, 69, 22–33. [Google Scholar] [CrossRef]
- Murphy, S.M.; Laura, M.; Fawcett, K.; Pandraud, A.; Liu, Y.T.; Davidson, G.L.; Rossor, A.M.; Polke, J.M.; Castleman, V.; Manji, H.; et al. Charcot-Marie-Tooth disease: Frequency of genetic subtypes and guidelines for genetic testing. J. Neurol. Neurosurg. Psychiatry 2012, 83, 706–710. [Google Scholar] [CrossRef]
- Divincenzo, C.; Elzinga, C.D.; Medeiros, A.C.; Karbassi, I.; Jones, J.R.; Evans, M.C.; Braastad, C.D.; Bishop, C.M.; Jaremko, M.; Wang, Z.; et al. The allelic spectrum of charcot–marie–tooth disease in over 17,000 individuals with neuropathy. Mol. Genet. Genomic Med. 2014, 2, 522–529. [Google Scholar] [CrossRef]
- Fridman, V.; Bundy, B.; Reilly, M.M.; Pareyson, D.; Bacon, C.; Burns, J.; Day, J.; Feely, S.; Finkel, R.S.; Grider, T.; et al. CMT subtypes and disease burden in patients enrolled in the Inherited Neuropathies Consortium natural history study: A cross-sectional analysis. J. Neurol. Neurosurg. Psychiatry 2015, 86, 873–878. [Google Scholar] [CrossRef] [Green Version]
- Lorefice, L.; Murru, M.R.; Coghe, G.; Fenu, G.; Corongiu, D.; Frau, J.; Tranquilli, S.; Tacconi, P.; Vannelli, A.; Marrosu, G.; et al. Charcot–Marie–Tooth disease: Genetic subtypes in the Sardinian population. Neurol. Sci. 2017, 38, 1019–1025. [Google Scholar] [CrossRef] [PubMed]
- Milley, G.M.; Varga, E.T.; Grosz, Z.; Nemes, C.; Arányi, Z.; Boczán, J.; Diószeghy, P.; Molnár, M.J.; Gál, A. Genotypic and phenotypic spectrum of the most common causative genes of Charcot-Marie-Tooth disease in Hungarian patients. Neuromuscul. Disord. 2018, 28, 38–43. [Google Scholar] [CrossRef] [PubMed]
- Manganelli, F.; Tozza, S.; Pisciotta, C.; Bellone, E.; Iodice, R.; Nolano, M.; Geroldi, A.; Capponi, S.; Mandich, P.; Santoro, L. Charcot-Marie-Tooth disease: Frequency of genetic subtypes in a Southern Italy population. J. Peripher. Nerv. Syst. 2014, 19, 292–298. [Google Scholar] [CrossRef] [PubMed]
- Sivera, R.; Sevilla, T.; Vílchez, J.J.; Martínez-Rubio, D.; Chumillas, M.J.; Vázquez, J.F.; Muelas, N.; Bataller, L.; Millán, J.M.; Palau, F.; et al. Charcot-Marie-Tooth disease: Genetic and clinical spectrum in a Spanish clinical series. Neurology 2013, 81, 1617–1625. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gentile, L.; Russo, M.; Fabrizi, G.M.; Taioli, F.; Ferrarini, M.; Testi, S.; Alfonzo, A.; Aguennouz, M.H.; Toscano, A.; Vita, G.; et al. Charcot-Marie-Tooth disease: Experience from a large Italian tertiary neuromuscular center. Neurol. Sci. 2020, 41, 1239–1243. [Google Scholar] [CrossRef] [PubMed]
- Echaniz-Laguna, A.; Geuens, T.; Petiot, P.; Péréon, Y.; Adriaenssens, E.; Haidar, M.; Capponi, S.; Maisonobe, T.; Fournier, E.; Dubourg, O.; et al. Axonal Neuropathies due to Mutations in Small Heat Shock Proteins: Clinical, Genetic, and Functional Insights into Novel Mutations. Hum. Mutat. 2017, 38, 556–568. [Google Scholar] [CrossRef]
- Sanmaneechai, O.; Feely, S.; Scherer, S.S.; Herrmann, D.N.; Burns, J.; Muntoni, F.; Li, J.; Siskind, C.E.; Day, J.W.; Laura, M.; et al. Genotype-phenotype characteristics and baseline natural history of heritable neuropathies caused by mutations in the MPZ gene. Brain 2015, 138 Pt 11, 3180–3192. [Google Scholar] [CrossRef] [Green Version]
- Callegari, I.; Gemelli, C.; Geroldi, A.; Veneri, F.; Mandich, P.; D’Antonio, M.; Pareyson, D.; Shy, M.E.; Schenone, A.; Prada, V.; et al. Mutation update for myelin protein zero-related neuropathies and the increasing role of variants causing a late-onset phenotype. J. Neurol. 2019, 266, 2629–2645. [Google Scholar] [CrossRef]
- Houlden, H.; Laura, M.; Wavrant-De Vrièze, F.; Blake, J.; Wood, N.; Reilly, M.M. Mutations in the HSP27 (HSPB1) gene cause dominant, recessive, and sporadic distal HMN/CMT type 2. Neurology 2008, 71, 1660–1668. [Google Scholar] [CrossRef]
- Pipis, M.; Rossor, A.M.; Laura, M.; Reilly, M.M. Next-generation sequencing in Charcot–Marie–Tooth disease: Opportunities and challenges. Nat. Rev. Neurol. 2019, 15, 644–656. [Google Scholar] [CrossRef]
- Regier, A.A.; Farjoun, Y.; Larson, D.E.; Krasheninina, O.; Kang, H.M.; Howrigan, D.P.; Chen, B.J.; Kher, M.; Banks, E.; Ames, D.C.; et al. Functional equivalence of genome sequencing analysis pipelines enables harmonized variant calling across human genetics projects. Nat. Commun. 2018, 9, 4038. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cortese, A.; Callegari, I.; Curro, R.; Vegezzi, E.; Colnaghi, S.; Versino, M.; Alfonsi, E.; Cosentino, G.; Valente, E.; Gana, S.; et al. Mutation in RNF170 causes sensory ataxic neuropathy with vestibular areflexia: A CANVAS mimic. J. Neurol. Neurosurg. Psychiatry 2020, 91, 1237–1238. [Google Scholar] [CrossRef] [PubMed]
- Cortese, A.; Curro’, R.; Vegezzi, E.; Yau, W.Y.; Houlden, H.; Reilly, M.M. Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS): Genetic and clinical aspects. Pract. Neurol. 2022, 22, 14–18. [Google Scholar] [CrossRef] [PubMed]
- Westra, D.; Schouten, M.I.; Stunnenberg, B.C.; Kusters, B.; Saris, C.G.J.; Erasmus, C.E.; Van Engelen, B.G.; Bulk, S.; Verschuuren-Bemelmans, C.C.; Gerkes, E.H.; et al. Panel-based exome sequencing for neuromuscular disorders as a diagnostic service. J. Neuromuscul. Dis. 2019, 6, 241–258. [Google Scholar] [CrossRef] [PubMed]
- Beecroft, S.J.; Lamont, P.J.; Edwards, S.; Goullée, H.; Davis, M.R.; Laing, N.G.; Ravenscroft, G. The Impact of Next-Generation Sequencing on the Diagnosis, Treatment, and Prevention of Hereditary Neuromuscular Disorders. Mol. Diagnosis Ther. 2020, 24, 641–652. [Google Scholar] [CrossRef]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Gemelli, C.; Geroldi, A.; Massucco, S.; Trevisan, L.; Callegari, I.; Marinelli, L.; Ursino, G.; Hamedani, M.; Mennella, G.; Stara, S.; et al. Genetic Workup for Charcot–Marie–Tooth Neuropathy: A Retrospective Single-Site Experience Covering 15 Years. Life 2022, 12, 402. https://doi.org/10.3390/life12030402
Gemelli C, Geroldi A, Massucco S, Trevisan L, Callegari I, Marinelli L, Ursino G, Hamedani M, Mennella G, Stara S, et al. Genetic Workup for Charcot–Marie–Tooth Neuropathy: A Retrospective Single-Site Experience Covering 15 Years. Life. 2022; 12(3):402. https://doi.org/10.3390/life12030402
Chicago/Turabian StyleGemelli, Chiara, Alessandro Geroldi, Sara Massucco, Lucia Trevisan, Ilaria Callegari, Lucio Marinelli, Giulia Ursino, Mehrnaz Hamedani, Giulia Mennella, Silvia Stara, and et al. 2022. "Genetic Workup for Charcot–Marie–Tooth Neuropathy: A Retrospective Single-Site Experience Covering 15 Years" Life 12, no. 3: 402. https://doi.org/10.3390/life12030402