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Novel mutation in CNTNAP1 results in congenital hypomyelinating neuropathy
Author(s) -
Mehta Paulomi,
Küspert Melanie,
Bale Tejus,
Brownstein Catherine A.,
Towne Meghan C.,
Girolami Umberto,
Shi Jiahai,
Beggs Alan H.,
Darras Basil T.,
Wegner Michael,
Piao Xianhua,
Agrawal Pankaj B.
Publication year - 2017
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.25416
Subject(s) - frameshift mutation , missense mutation , exome sequencing , proband , mutation , genetics , nerve biopsy , muscle biopsy , medicine , biology , gene , endocrinology , biopsy , peripheral neuropathy , diabetes mellitus
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