Gal Moran, Magen Daniella, Zahran Younan, Ravid Sarit, Eran Ayelet, Khayat Morad, Gafni Chen, Levanon Erez Y, Mandel Hanna
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan Israel.
Pediatric Nephrology Institute, Rambam Health Care Campus, Haifa, Israel; Laboratory of Molecular Medicine, Rappaport School of Medicine, Technion, Haifa, Israel.
Eur J Med Genet. 2016 Apr;59(4):204-9. doi: 10.1016/j.ejmg.2016.02.007. Epub 2016 Feb 23.
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.
我们研究了三名近亲结婚父母所生的兄弟姐妹，他们患有严重智力残疾、恶病质、斜视、癫痫以及异常呼吸节律发作。全外显子组测序导致在NALCN基因中鉴定出一种新的纯合剪接位点突变，IVS29-1G>A，该突变导致患者出现异常转录本。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。此前仅在8例患有严重肌张力减退、言语障碍、认知延迟、便秘和婴儿神经轴索性营养不良样症状的患者中鉴定出NALCN基因的三个纯合突变。我们的患者拓宽了与NALCN隐性突变相关的临床谱，其特征还包括模仿纯合Nalcn基因敲除小鼠的呼吸节律紊乱。
