Journal of Genetic Medicine

  • 제17권2호
  • /
  • Pages.89-91
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  • 2020
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  • 1226-1769(pISSN)
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  • 2383-8442(eISSN)
대한의학유전학회 (Korean Society of Medical Genetics and Genomics)
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Axonal Charcot-Marie-Tooth case with a novel heterozygous variant in MFN2 assessed by the MutationDistiller

  • Ryu, Ho-Sung (Department of Neurology, Kyungpook National University Hospital) ;
  • Lee, Yun-Jeong (Department of Pediatrics, School of Medicine, Kyungpook National University, Kyungpook National University Hospital) ;
  • Lee, Jong-Mok (Department of Neurology, Kyungpook National University Hospital)
  • 투고 : 2020.07.03
  • 심사 : 2020.07.21
  • 발행 : 2020.12.31
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초록

Charcot-Marie-Tooth (CMT) disease can be divided mainly into demyelination and axonopathy based on the results of the electrophysiological study. Mitofusin 2, encoded by MFN2 gene, has a crucial role in the fusion of mitochondria, which is known to associate with CMT type 2A as one of the axonal forms. We describe a 44-year-old man with progressive weakness on bilateral legs after noticing foot drop in his early teen. When we examined him at 45 years of age, he presented atrophy on entire legs and with distal muscle weakness on limbs. The nerve conduction study revealed severely decreased amplitude on motor nerve ranging from 0.2 to 4.5 mV, while conduction velocity remained more than 30.4 m/s. The whole-exome sequencing revealed a novel variant c.2228G>T in MFN2 by efficient genetic analysis tool, MutationDistiller. This report will not only expand the mutation spectrum of CMT2A but also introduce a time-saving genetic analysis tool.

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참고문헌

  1. Bombelli F, Stojkovic T, Dubourg O, Echaniz-Laguna A, Tardieu S, Larcher K, et al. Charcot-Marie-Tooth disease type 2A: from typical to rare phenotypic and genotypic features. JAMA Neurol 2014;71:1036-42. https://doi.org/10.1001/jamaneurol.2014.629
  2. Filadi R, Pendin D, Pizzo P. Mitofusin 2: from functions to disease. Cell Death Dis 2018;9:330. https://doi.org/10.1038/s41419-017-0023-6
  3. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al.; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015;17:405-24. https://doi.org/10.1038/gim.2015.30
  4. Hombach D, Schuelke M, Knierim E, Ehmke N, Schwarz JM, Fischer-Zirnsak B, et al. MutationDistiller: user-driven identification of pathogenic DNA variants. Nucleic Acids Res 2019;47:W114-20. https://doi.org/10.1093/nar/gkz330
  5. Choi BO, Nakhro K, Park HJ, Hyun YS, Lee JH, Kanwal S, et al. A cohort study of MFN2 mutations and phenotypic spectrums in Charcot-Marie-Tooth disease 2A patients. Clin Genet 2015;87:594-8. https://doi.org/10.1111/cge.12432
  6. Verhoeven K, Claeys KG, Züchner S, Schroder JM, Weis J, Ceuterick C, et al. MFN2 mutation distribution and genotype/phenotype correlation in Charcot-Marie-Tooth type 2. Brain 2006;129(Pt 8):2093-102. https://doi.org/10.1093/brain/awl126
  7. Chung KW, Kim SB, Park KD, Choi KG, Lee JH, Eun HW, et al. Early onset severe and late-onset mild Charcot-Marie-Tooth disease with mitofusin 2 (MFN2) mutations. Brain 2006;129(Pt 8):2103-18. https://doi.org/10.1093/brain/awl174