Contactin-Associated Protein 1 (CNTNAP1) Mutations Induce Characteristic Lesions of the Paranodal Region

Jean Michel Vallat, Mathilde Nizon, Alex Magee, Bertrand Isidor, Laurent Magy, Yann Péréon, Laurence Richard, Robert Ouvrier, Benjamin Cogné, Jérôme Devaux, Stephan L Zuchner, Stéphane Mathis

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Congenital hypomyelinating neuropathy is a rare neonatal syndrome responsible for hypotonia and weakness. Nerve microscopic examination shows amyelination or hypomyelination. Recently, mutations in CNTNAP1 have been described in a few patients. CNTNAP1 encodes contactin-associated protein 1 (caspr-1), which is an essential component of the paranodal junctions of the peripheral and central nervous systems, and is necessary for the establishment of transverse bands that stabilize paranodal axo-glial junctions. We present the results of nerve biopsy studies of three patients from two unrelated, non-consanguineous families with compound heterozygous CNTNAP1 mutations. The lesions were identical, characterized by a hypomyelinating process; on electron microscopy, we detected, in all nodes of Ranvier, subtle lesions that have never been previously described in human nerves. Transverse bands of the myelin loops were absent, with a loss of attachment between myelin and the axolemma; elongated Schwann cell processes sometimes dissociated the Schwann cell and axon membranes that bound the space between them. These lesions were observed in the area where caspr-1 is located and are reminiscent of the lesions reported in sciatic nerves of caspr-1 null mice. CNTNAP1 mutations appear to induce characteristic ultrastructural lesions of the paranodal region.

Original languageEnglish (US)
Pages (from-to)1155-1159
Number of pages5
JournalJournal of Neuropathology and Experimental Neurology
Volume75
Issue number12
DOIs
StatePublished - Dec 1 2016

Keywords

  • CNTNAP1
  • Contactin
  • Nerve biopsy
  • Node of Ranvier.

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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  • Cite this

    Vallat, J. M., Nizon, M., Magee, A., Isidor, B., Magy, L., Péréon, Y., Richard, L., Ouvrier, R., Cogné, B., Devaux, J., Zuchner, S. L., & Mathis, S. (2016). Contactin-Associated Protein 1 (CNTNAP1) Mutations Induce Characteristic Lesions of the Paranodal Region. Journal of Neuropathology and Experimental Neurology, 75(12), 1155-1159. https://doi.org/10.1093/jnen/nlw093