A novel homozygous splice site mutation in NALCN identified in siblings with cachexia, strabismus, severe intellectual disability, epilepsy and abnormal respiratory rhythm
A novel homozygous splice site mutation in NALCN identified in siblings with cachexia, strabismus, severe intellectual disability, epilepsy and abnormal respiratory rhythm
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DOI：
10.1016/j.ejmg.2016.02.007
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发表时间：
2016-04-01
影响因子：
1.9
通讯作者：
Mandel, Hanna
中科院分区：
文献类型：
--
作者：
Gal, Moran;Magen, Daniella;Mandel, Hanna
我们研究了三个兄弟姐妹，他们的父母是近亲，他们表现为严重的智力残疾、恶病质、斜视、癫痫发作和呼吸节律异常。全外显子组测序导致鉴定出NALCN基因中的新纯合剪接位点突变IVS 29 -1G > A，其导致患者中的异常转录物。NALCN编码一种电压非依赖性阳离子通道，参与神经元兴奋性的调节。NALCN基因中的三个纯合突变先前仅在8名患有严重张力减退、言语障碍、认知延迟、便秘和婴儿神经轴突营养不良样症状的患者中被鉴定。我们的患者拓宽了与NALCN隐性突变相关的临床谱，其特征还在于模仿纯合Nalcn敲除小鼠的呼吸节律中断。(C)2016 Elsevier Masson SAS。All rights reserved.
We studied three siblings, born to consanguineous parents who presented with severe intellectual disability, cachexia, strabismus, seizures and episodes of abnormal respiratory rhythm. Whole exome sequencing led to identification of a novel homozygous splice site mutation, IVS29-1G > A in the NALCN gene, that resulted in aberrant transcript in the patients. NALCN encodes a voltage-independent cation channel, involved in regulation of neuronal excitability. Three homozygous mutations in the NALCN gene were previously identified in only eight patients with severe hypotonia, speech impairment, cognitive delay, constipation and Infantile-Neuroaxonal-dystrophy- like symptoms. Our patients broaden the clinical spectrum associated with recessive mutations in NALCN, featuring also disrupted respiratory rhythm mimicking homozygous Nalcn knockout mice. (C) 2016 Elsevier Masson SAS. All rights reserved.