Skip to main content
PMC home page
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 1999 Feb;66(2):202–206. doi: 10.1136/jnnp.66.2.202

Central visual, acoustic, and motor pathway involvement in a Charcot-Marie-Tooth family with an Asn205Ser mutation in the connexin 32 gene

M Bahr 1, F Andres 1, V Timmerman 1, M Nelis 1, C Van Broeckhoven 1, J Dichgans 1
PMCID: PMC1736220  PMID: 10071100

Abstract

BACKGROUND—X linked dominant Charcot-Marie-Tooth disease (CMT1X) is an inherited motor and sensory neuropathy that mainly affects the peripheral nervous system. CMT1X is associated with mutations in the gap junction protein connexin 32 (Cx32). Cx32 is expressed in Schwann cells and oligodendrocytes in the peripheral (PNS) and in the (CNS) respectively.
METHODS—A CMT1X family with a Cx32 mutation was examined clinically and electrophysiologically to determine whether PNS, or CNS, or both pathways were affected.
RESULTS—In a CMT1X family a novel mutation (Asn205Ser) was found in the fourth transmembrane domain of Cx32. The patients showed typical clinical and electrophysiological abnormalities in the PNS, but in addition visual, acoustic, and motor pathways of the CNS were affected subclinically. This was indicated by pathological changes in visually evoked potentials (VEPs), brainstem auditory evoked potentials (BAEPs), and central motor evoked potentials (CMEPs).
CONCLUSIONS—These findings underscore the necessity of a careful analysis of CNS pathways in patients with CMT and Cx32 mutations. Abnormal electrophysiological findings in CNS pathway examinations should raise the suspicion of CMTX and a search for gene mutations towards Cx32 should be considered.



Full Text

The Full Text of this article is available as a PDF (124.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bennett M. V., Barrio L. C., Bargiello T. A., Spray D. C., Hertzberg E., Sáez J. C. Gap junctions: new tools, new answers, new questions. Neuron. 1991 Mar;6(3):305–320. doi: 10.1016/0896-6273(91)90241-q. [DOI] [PubMed] [Google Scholar]
  2. Bergoffen J., Scherer S. S., Wang S., Scott M. O., Bone L. J., Paul D. L., Chen K., Lensch M. W., Chance P. F., Fischbeck K. H. Connexin mutations in X-linked Charcot-Marie-Tooth disease. Science. 1993 Dec 24;262(5142):2039–2042. doi: 10.1126/science.8266101. [DOI] [PubMed] [Google Scholar]
  3. Bruzzone R., White T. W., Scherer S. S., Fischbeck K. H., Paul D. L. Null mutations of connexin32 in patients with X-linked Charcot-Marie-Tooth disease. Neuron. 1994 Nov;13(5):1253–1260. doi: 10.1016/0896-6273(94)90063-9. [DOI] [PubMed] [Google Scholar]
  4. Carroll W. M., Jones S. J., Halliday A. M. Visual evoked potential abnormalities in Charcot-Marie-Tooth disease and comparison with Friedreich's ataxia. J Neurol Sci. 1983 Sep;61(1):123–133. doi: 10.1016/0022-510x(83)90059-x. [DOI] [PubMed] [Google Scholar]
  5. Chance P. F., Fischbeck K. H. Molecular genetics of Charcot-Marie-Tooth disease and related neuropathies. Hum Mol Genet. 1994;3(Spec No):1503–1507. doi: 10.1093/hmg/3.suppl_1.1503. [DOI] [PubMed] [Google Scholar]
  6. De Jonghe P., Timmerman V., Nelis E., Martin J. J., Van Broeckhoven C. Charcot-Marie-Tooth disease and related peripheral neuropathies. J Peripher Nerv Syst. 1997;2(4):370–387. [PubMed] [Google Scholar]
  7. Dermietzel R., Farooq M., Kessler J. A., Althaus H., Hertzberg E. L., Spray D. C. Oligodendrocytes express gap junction proteins connexin32 and connexin45. Glia. 1997 Jun;20(2):101–114. [PubMed] [Google Scholar]
  8. Dermietzel R., Spray D. C. Gap junctions in the brain: where, what type, how many and why? Trends Neurosci. 1993 May;16(5):186–192. doi: 10.1016/0166-2236(93)90151-b. [DOI] [PubMed] [Google Scholar]
  9. Hahn A. F., Brown W. F., Koopman W. J., Feasby T. E. X-linked dominant hereditary motor and sensory neuropathy. Brain. 1990 Oct;113(Pt 5):1511–1525. doi: 10.1093/brain/113.5.1511. [DOI] [PubMed] [Google Scholar]
  10. Harding A. E., Thomas P. K. Genetic aspects of hereditary motor and sensory neuropathy (types I and II). J Med Genet. 1980 Oct;17(5):329–336. doi: 10.1136/jmg.17.5.329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ionasescu V. V. Charcot-Marie-Tooth neuropathies: from clinical description to molecular genetics. Muscle Nerve. 1995 Mar;18(3):267–275. doi: 10.1002/mus.880180302. [DOI] [PubMed] [Google Scholar]
  12. Janssen E. A., Kemp S., Hensels G. W., Sie O. G., de Die-Smulders C. E., Hoogendijk J. E., de Visser M., Bolhuis P. A. Connexin32 gene mutations in X-linked dominant Charcot-Marie-Tooth disease (CMTX1). Hum Genet. 1997 Apr;99(4):501–505. doi: 10.1007/s004390050396. [DOI] [PubMed] [Google Scholar]
  13. Jones S. J., Carroll W. M., Halliday A. M. Peripheral and central sensory nerve conduction in Charcot-Marie-Tooth disease and comparison with Friedreich's ataxia. J Neurol Sci. 1983 Sep;61(1):135–148. doi: 10.1016/0022-510x(83)90060-6. [DOI] [PubMed] [Google Scholar]
  14. Li J., Hertzberg E. L., Nagy J. I. Connexin32 in oligodendrocytes and association with myelinated fibers in mouse and rat brain. J Comp Neurol. 1997 Mar 24;379(4):571–591. doi: 10.1002/(sici)1096-9861(19970324)379:4<571::aid-cne8>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]
  15. Nadarajah B., Thomaidou D., Evans W. H., Parnavelas J. G. Gap junctions in the adult cerebral cortex: regional differences in their distribution and cellular expression of connexins. J Comp Neurol. 1996 Dec 9;376(2):326–342. doi: 10.1002/(SICI)1096-9861(19961209)376:2<326::AID-CNE13>3.0.CO;2-J. [DOI] [PubMed] [Google Scholar]
  16. Nelis E., Simokovic S., Timmerman V., Löfgren A., Backhovens H., De Jonghe P., Martin J. J., Van Broeckhoven C. Mutation analysis of the connexin 32 (Cx32) gene in Charcot-Marie-Tooth neuropathy type 1: identification of five new mutations. Hum Mutat. 1997;9(1):47–52. doi: 10.1002/(SICI)1098-1004(1997)9:1<47::AID-HUMU8>3.0.CO;2-M. [DOI] [PubMed] [Google Scholar]
  17. Nicholson G., Corbett A. Slowing of central conduction in X-linked Charcot-Marie-Tooth neuropathy shown by brain stem auditory evoked responses. J Neurol Neurosurg Psychiatry. 1996 Jul;61(1):43–46. doi: 10.1136/jnnp.61.1.43. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Scaioli V., Pareyson D., Avanzini G., Sghirlanzoni A. F response and somatosensory and brainstem auditory evoked potential studies in HMSN type I and II. J Neurol Neurosurg Psychiatry. 1992 Nov;55(11):1027–1031. doi: 10.1136/jnnp.55.11.1027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Thomas P. K., King R. H., Small J. R., Robertson A. M. The pathology of charcot-marie-tooth disease and related disorders. Neuropathol Appl Neurobiol. 1996 Aug;22(4):269–284. doi: 10.1111/j.1365-2990.1996.tb01105.x. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

RESOURCES