Novel mutation in CNTNAP1 results in congenital hypomyelinating neuropathy
- Muscle Nerve. 2017 May;55(5):761-765. doi: 10.1002/mus.25416.
- 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.
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.