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. 2000 Dec;69(6):806–811. doi: 10.1136/jnnp.69.6.806

An axonal form of Charcot-Marie-Tooth disease showing distinctive features in association with mutations in the peripheral myelin protein zero gene (Thr124Met or Asp75Val)

K Misu 1, T Yoshihara 1, Y Shikama 1, E Awaki 1, M Yamamoto 1, N Hattori 1, M Hirayama 1, T Takegami 1, K Nakashima 1, G Sobue 1
PMCID: PMC1737183  PMID: 11080237

Abstract

OBJECTIVES AND METHODS—Seven families were studied with an axonal form of Charcot-Marie-Tooth disease (CMT) associated with mutations in the peripheral myelin protein zero (MPZ) gene—Thr124Met or Asp75Val.
RESULTS—Patients with these mutations commonly showed relatively late onset sensorimotor neuropathy predominantly involving the lower limbs. Sensory impairment typically was marked, and distal muscle atrophy and weakness were also present in the legs. Adie's pupil and deafness were often present, and serum creatine kinase concentrations were often raised irrespective of which MPZ mutation was present. Relatively well preserved motor and sensory nerve conduction velocities contrasted with reduced or absent compound muscle action potentials and sensory nerve action potentials. Axonal change with marked axonal sprouting was seen in sural nerve specimens.
CONCLUSION—The similar associated clinical findings suggest that patients with axonal CMT with an MPZ gene mutation share distinctive clinical features.



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Selected References

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  1. Ben Othmane K., Middleton L. T., Loprest L. J., Wilkinson K. M., Lennon F., Rozear M. P., Stajich J. M., Gaskell P. C., Roses A. D., Pericak-Vance M. A. Localization of a gene (CMT2A) for autosomal dominant Charcot-Marie-Tooth disease type 2 to chromosome 1p and evidence of genetic heterogeneity. Genomics. 1993 Aug;17(2):370–375. doi: 10.1006/geno.1993.1334. [DOI] [PubMed] [Google Scholar]
  2. Chapon F., Latour P., Diraison P., Schaeffer S., Vandenberghe A. Axonal phenotype of Charcot-Marie-Tooth disease associated with a mutation in the myelin protein zero gene. J Neurol Neurosurg Psychiatry. 1999 Jun;66(6):779–782. doi: 10.1136/jnnp.66.6.779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. De Jonghe P., Timmerman V., Ceuterick C., Nelis E., De Vriendt E., Löfgren A., Vercruyssen A., Verellen C., Van Maldergem L., Martin J. J. The Thr124Met mutation in the peripheral myelin protein zero (MPZ) gene is associated with a clinically distinct Charcot-Marie-Tooth phenotype. Brain. 1999 Feb;122(Pt 2):281–290. doi: 10.1093/brain/122.2.281. [DOI] [PubMed] [Google Scholar]
  4. Griffin J. W., Cornblath D. R., Alexander E., Campbell J., Low P. A., Bird S., Feldman E. L. Ataxic sensory neuropathy and dorsal root ganglionitis associated with Sjögren's syndrome. Ann Neurol. 1990 Mar;27(3):304–315. doi: 10.1002/ana.410270313. [DOI] [PubMed] [Google Scholar]
  5. Harding A. E., Thomas P. K. The clinical features of hereditary motor and sensory neuropathy types I and II. Brain. 1980 Jun;103(2):259–280. doi: 10.1093/brain/103.2.259. [DOI] [PubMed] [Google Scholar]
  6. Hattori N., Ichimura M., Nagamatsu M., Li M., Yamamoto K., Kumazawa K., Mitsuma T., Sobue G. Clinicopathological features of Churg-Strauss syndrome-associated neuropathy. Brain. 1999 Mar;122(Pt 3):427–439. doi: 10.1093/brain/122.3.427. [DOI] [PubMed] [Google Scholar]
  7. Hayasaka K., Himoro M., Sato W., Takada G., Uyemura K., Shimizu N., Bird T. D., Conneally P. M., Chance P. F. Charcot-Marie-Tooth neuropathy type 1B is associated with mutations of the myelin P0 gene. Nat Genet. 1993 Sep;5(1):31–34. doi: 10.1038/ng0993-31. [DOI] [PubMed] [Google Scholar]
  8. Ionasescu V., Searby C., Sheffield V. C., Roklina T., Nishimura D., Ionasescu R. Autosomal dominant Charcot-Marie-Tooth axonal neuropathy mapped on chromosome 7p (CMT2D). Hum Mol Genet. 1996 Sep;5(9):1373–1375. doi: 10.1093/hmg/5.9.1373. [DOI] [PubMed] [Google Scholar]
  9. Kwon J. M., Elliott J. L., Yee W. C., Ivanovich J., Scavarda N. J., Moolsintong P. J., Goodfellow P. J. Assignment of a second Charcot-Marie-Tooth type II locus to chromosome 3q. Am J Hum Genet. 1995 Oct;57(4):853–858. [PMC free article] [PubMed] [Google Scholar]
  10. Marrosu M. G., Vaccargiu S., Marrosu G., Vannelli A., Cianchetti C., Muntoni F. Charcot-Marie-Tooth disease type 2 associated with mutation of the myelin protein zero gene. Neurology. 1998 May;50(5):1397–1401. doi: 10.1212/wnl.50.5.1397. [DOI] [PubMed] [Google Scholar]
  11. Misu K. i., Hattori N., Nagamatsu M., Ikeda S. i., Ando Y., Nakazato M., Takei Y. i., Hanyu N., Usui Y., Tanaka F. Late-onset familial amyloid polyneuropathy type I (transthyretin Met30-associated familial amyloid polyneuropathy) unrelated to endemic focus in Japan. Clinicopathological and genetic features. Brain. 1999 Oct;122(Pt 10):1951–1962. doi: 10.1093/brain/122.10.1951. [DOI] [PubMed] [Google Scholar]
  12. Nelis E., Haites N., Van Broeckhoven C. Mutations in the peripheral myelin genes and associated genes in inherited peripheral neuropathies. Hum Mutat. 1999;13(1):11–28. doi: 10.1002/(SICI)1098-1004(1999)13:1<11::AID-HUMU2>3.0.CO;2-A. [DOI] [PubMed] [Google Scholar]
  13. Sobue G., Hashizume Y., Mukai E., Hirayama M., Mitsuma T., Takahashi A. X-linked recessive bulbospinal neuronopathy. A clinicopathological study. Brain. 1989 Feb;112(Pt 1):209–232. doi: 10.1093/brain/112.1.209. [DOI] [PubMed] [Google Scholar]
  14. Sobue G., Li M., Terao S., Aoki S., Ichimura M., Ieda T., Doyu M., Yasuda T., Hashizume Y., Mitsuma T. Axonal pathology in Japanese Guillain-Barré syndrome: a study of 15 autopsied cases. Neurology. 1997 Jun;48(6):1694–1700. doi: 10.1212/wnl.48.6.1694. [DOI] [PubMed] [Google Scholar]
  15. Takashima H., Nakagawa M., Nakahara K., Suehara M., Matsuzaki T., Higuchi I., Higa H., Arimura K., Iwamasa T., Izumo S. A new type of hereditary motor and sensory neuropathy linked to chromosome 3. Ann Neurol. 1997 Jun;41(6):771–780. doi: 10.1002/ana.410410613. [DOI] [PubMed] [Google Scholar]
  16. Uyemura K., Asou H., Yazaki T., Takeda Y. Cell-adhesion proteins of the immunoglobulin superfamily in the nervous system. Essays Biochem. 1996;31:37–48. [PubMed] [Google Scholar]
  17. Warner L. E., Hilz M. J., Appel S. H., Killian J. M., Kolodry E. H., Karpati G., Carpenter S., Watters G. V., Wheeler C., Witt D. Clinical phenotypes of different MPZ (P0) mutations may include Charcot-Marie-Tooth type 1B, Dejerine-Sottas, and congenital hypomyelination. Neuron. 1996 Sep;17(3):451–460. doi: 10.1016/s0896-6273(00)80177-4. [DOI] [PubMed] [Google Scholar]
  18. Waterschoot M. P., Guerit J. M., Lambert M., de Barsy T. Bilateral tonic pupils and polyneuropathy in Sjögren's syndrome: a common pathophysiological mechanism? Eur Neurol. 1991;31(2):114–116. doi: 10.1159/000116657. [DOI] [PubMed] [Google Scholar]
  19. Yoshihara T., Yamamoto M., Doyu M., Mis K. I., Hattori N., Hasegawa Y., Mokuno K., Mitsuma T., Sobue G. Mutations in the peripheral myelin protein zero and connexin32 genes detected by non-isotopic RNase cleavage assay and their phenotypes in Japanese patients with Charcot-Marie-Tooth disease. Hum Mutat. 2000 Aug;16(2):177–178. doi: 10.1002/1098-1004(200008)16:2<177::AID-HUMU14>3.0.CO;2-5. [DOI] [PubMed] [Google Scholar]

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