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

Novel mutation in CNTNAP1 results in congenital hypomyelinating neuropathy.

Author information

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.

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

PMID:
27668699
PMCID:
PMC5366284
DOI:
10.1002/mus.25416
[Indexed for MEDLINE]
Free PMC Article

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