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GJB1-associated X-linked Charcot–Marie–Tooth disease, a disorder affecting the central and peripheral nervous systems

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Abstract

Charcot–Marie–Tooth disease (CMT) is a group of inherited diseases characterized by exclusive or predominant involvement of the peripheral nervous system. Mutations in GJB1, the gene encoding Connexin 32 (Cx32), a gap-junction channel forming protein, cause the most common X-linked form of CMT, CMT1X. Cx32 is expressed in Schwann cells and oligodendrocytes, the myelinating glia of the peripheral and central nervous systems, respectively. Thus, patients with CMT1X have both central and peripheral nervous system manifestations. Study of the genetics of CMT1X and the phenotypes of patients with this disorder suggest that the peripheral manifestations of CMT1X are likely to be due to loss of function, while in the CNS gain of function may contribute. Mice with targeted ablation of Gjb1 develop a peripheral neuropathy similar to that seen in patients with CMT1X, supporting loss of function as a mechanism for the peripheral manifestations of this disorder. Possible roles for Cx32 include the establishment of a reflexive gap junction pathway in the peripheral and central nervous system and of a panglial syncitium in the central nervous system.

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Acknowledgments

This work is supported by grants from the Muscular Dystrophy Association and the National Multiple Sclerosis Society.

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Authors and Affiliations

  1. Departments of Neurology and Physiology & Pharmacology, State University of New York, Brooklyn, NY, 11203, USA

    Charles K. Abrams

  2. The Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, 10461, USA

    Mona Freidin

  3. State University of New York, 450 Clarkson Avenue, Box 1213, Brooklyn, NY, 11203, USA

    Charles K. Abrams

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  1. Charles K. Abrams
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  2. Mona Freidin
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Correspondence to Charles K. Abrams.

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Abrams, C.K., Freidin, M. GJB1-associated X-linked Charcot–Marie–Tooth disease, a disorder affecting the central and peripheral nervous systems. Cell Tissue Res 360, 659–673 (2015). https://doi.org/10.1007/s00441-014-2014-6

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  • DOI: https://doi.org/10.1007/s00441-014-2014-6

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