CNTNAP1基因的新型突变导致先天性髓鞘形成不良性神经病。
Novel mutation in CNTNAP1 results in congenital hypomyelinating neuropathy.
作者信息
Mehta Paulomi, Küspert Melanie, Bale Tejus, Brownstein Catherine A, Towne Meghan C, De Girolami Umberto, Shi Jiahai, Beggs Alan H, Darras Basil T, Wegner Michael, Piao Xianhua, Agrawal Pankaj B
机构信息
Division of Newborn Medicine, Department of Medicine, Boston Children's Hospital, 300 Longwood Avenue, Harvard Medical School, Boston, Massachusetts, 02115, USA.
Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
出版信息
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.
引言
先天性髓鞘形成不足性神经病（CHN）是一种罕见的先天性神经病，在新生儿期发病，此前已与多个与髓鞘形成相关的基因突变有关。最近一项研究将接触蛋白相关蛋白1（CNTNAP1）基因中的4个纯合移码突变与此病症联系起来。
方法
我们报告了一名患有CHN的新生儿，其感觉神经和复合肌肉动作电位缺失，神经活检显示髓鞘形成不足。
结果
通过全外显子组测序，我们在先证者中鉴定出一种新的CNTNAP1纯合错义突变（p.Arg388Pro），其父母均为携带者。分子模型表明，该变体破坏了一条β链，导致结构不稳定，并可能使蛋白质功能发生显著变化。
结论
本报告将一个CNTNAP1错义变体与之前仅与移码突变相关的疾病表型联系起来。《肌肉与神经》55: 761 - 765, 2017年。
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