2. Academic Validation
  3. Novel mutation in CNTNAP1 results in congenital hypomyelinating neuropathy

Novel mutation in CNTNAP1 results in congenital hypomyelinating neuropathy

  • Muscle Nerve. 2017 May;55(5):761-765. doi: 10.1002/mus.25416.
Paulomi Mehta 1,  Melanie Küspert 2,  Tejus Bale 3,  Catherine A Brownstein 4 5,  Meghan C Towne 4 5,  Umberto De Girolami 3,  Jiahai Shi 6,  Alan H Beggs 4 5,  Basil T Darras 7,  Michael Wegner 2,  Xianhua Piao 1,  Pankaj B Agrawal 1 4 5
Affiliations

Affiliations

  • 1 Division of Newborn Medicine, Department of Medicine, Boston Children's Hospital, 300 Longwood Avenue, Harvard Medical School, Boston, Massachusetts, 02115, USA.
  • 2 Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
  • 3 Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • 4 Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • 5 The Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • 6 Department of Biomedical Sciences, City University of Hong Kong, Hong Kong.
  • 7 Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
PMID: 27668699 DOI: 10.1002/mus.25416
Abstract

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.

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