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 Zuchner, Stéphane Mathis

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


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
Issue number12
StatePublished - Dec 1 2016


  • 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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