Novel mutation in CNTNAP1 results in congenital hypomyelinating neuropathy

Muscle Nerve. 2017 May;55(5):761-765. doi: 10.1002/mus.25416. Epub 2017 Feb 3.


Introduction: Congenital hypomyelinating neuropathy (CHN) is a rare congenital neuropathy that presents in the neonatal period and has been linked previously to mutations in several genes associated with myelination. A recent study has linked 4 homozygous frameshift mutations in the contactin-associated protein 1 (CNTNAP1) gene with this condition.

Methods: We report a neonate with CHN who was found to have absent sensory nerve and compound muscle action potentials and hypomyelination on nerve biopsy.

Results: On whole exome sequencing, we identified a novel CNTNAP1 homozygous missense mutation (p.Arg388Pro) in the proband, and both parents were carriers. Molecular modeling suggests that this variant disrupts a β-strand to cause an unstable structure and likely significant changes in protein function.

Conclusions: This report links a missense CNTNAP1 variant to the disease phenotype previously associated only with frameshift mutations. Muscle Nerve 55: 761-765, 2017.

Keywords: CNTNAP1; congenital neuropathy; exome sequencing; hypomyelination; missense mutation; nerve conduction.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / physiology
  • Cell Adhesion Molecules, Neuronal / genetics*
  • Charcot-Marie-Tooth Disease / genetics*
  • Charcot-Marie-Tooth Disease / physiopathology
  • Electromyography
  • Fatal Outcome
  • Humans
  • Infant, Newborn
  • Male
  • Motor Neurons / physiology
  • Mutation, Missense*
  • Neural Conduction / physiology


  • CNTNAP1 protein, human
  • Cell Adhesion Molecules, Neuronal

Supplementary concepts

  • Charcot-Marie-Tooth disease, Type 4E