扩展与该基因相关的表型和基因缺陷
Expanding the Phenotype and Genetic Defects Associated with the Gene.
作者信息
Praschberger Roman, Balint Bettina, Mencacci Niccolo E, Hersheson Joshua, Rubio-Agusti Ignacio, Kullmann Dimitri M, Bettencourt Conceição, Bhatia Kailash, Houlden Henry
机构信息
Department of Molecular Neuroscience UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery (NHNN) London United Kingdom.
Department of Clinical and Experimental Epilepsy UCL Institute of Neurology London United Kingdom.
出版信息
Mov Disord Clin Pract. 2015 Jun 17;2(3):271-273. doi: 10.1002/mdc3.12190. eCollection 2015 Sep.
Abstract
BACKGROUND
The homozygous missense mutation c.430G>T (p.G144W) in the gene has been repeatedly shown to cause progressive myoclonus epilepsy/ataxia. Thus far, no other disease associated mutation has been reported.
METHODS
From epilepsy, movement disorder and genetic clinics 43 patients suffering from progressive myoclonus epilepsy/ataxia were screened for defects in and .
RESULTS
A 61-year-old female patient suffering from progressive myoclonus epilepsy was found to be compound heterozygous for the known c.430G>T and a novel c.491_493delAGA (p.K164del) mutation. This is so far the oldest patient and her disease course seems overall milder.
CONCLUSIONS
This finding further highlights the gene as a cause of progressive myoclonus epilepsy and expands the genotype for a potentially weaker disease allele.
摘要
背景
该基因中的纯合错义突变c.430G>T（p.G144W）已被反复证明可导致进行性肌阵挛癫痫/共济失调。迄今为止，尚未报道其他与疾病相关的突变。
方法
从癫痫、运动障碍和遗传诊所中，对43例患有进行性肌阵挛癫痫/共济失调的患者进行了该基因缺陷筛查。
结果
一名患有进行性肌阵挛癫痫的61岁女性患者被发现为已知的c.430G>T和一个新的c.491_493delAGA（p.K164del）突变的复合杂合子。这是迄今为止年龄最大的患者，其病程似乎总体较为轻微。
结论
这一发现进一步突出了该基因是进行性肌阵挛癫痫的病因，并扩展了可能具有较弱疾病等位基因的基因型。
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本文引用的文献
1
A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy.KCNC1基因中的一种复发性新生突变导致进行性肌阵挛癫痫。
Nat Genet. 2015 Jan;47(1):39-46. doi: 10.1038/ng.3144. Epub 2014 Nov 17.
2
Ramsay Hunt syndrome: clinical characterization of progressive myoclonus ataxia caused by GOSR2 mutation.拉姆齐亨特综合征：GOSR2 突变导致进行性肌阵挛小脑共济失调的临床特征。
Mov Disord. 2014 Jan;29(1):139-43. doi: 10.1002/mds.25704. Epub 2013 Oct 30.
3
'North Sea' progressive myoclonus epilepsy: phenotype of subjects with GOSR2 mutation.北海进行性肌阵挛性癫痫：GOSR2 突变患者的表型。
Brain. 2013 Apr;136(Pt 4):1146-54. doi: 10.1093/brain/awt021. Epub 2013 Feb 28.
4
Genetics of epilepsy and relevance to current practice.癫痫的遗传学及其与当前实践的相关性。
Curr Neurol Neurosci Rep. 2012 Aug;12(4):445-55. doi: 10.1007/s11910-012-0281-8.
5
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6
A homozygous mutation in human PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy-ataxia syndrome.人类PRICKLE1基因的纯合突变导致常染色体隐性进行性肌阵挛癫痫共济失调综合征。
Am J Hum Genet. 2008 Nov;83(5):572-81. doi: 10.1016/j.ajhg.2008.10.003. Epub 2008 Oct 30.
7
A nonsense mutation in the LIMP-2 gene associated with progressive myoclonic epilepsy and nephrotic syndrome.与进行性肌阵挛癫痫和肾病综合征相关的LIMP-2基因中的无义突变。
Hum Mol Genet. 2008 Jul 15;17(14):2238-43. doi: 10.1093/hmg/ddn124. Epub 2008 Apr 17.
8
Array-based gene discovery with three unrelated subjects shows SCARB2/LIMP-2 deficiency causes myoclonus epilepsy and glomerulosclerosis.对三名无亲缘关系的受试者进行基于基因芯片的基因发现研究表明，SCARB2/LIMP-2缺陷会导致肌阵挛性癫痫和肾小球硬化。
Am J Hum Genet. 2008 Mar;82(3):673-84. doi: 10.1016/j.ajhg.2007.12.019. Epub 2008 Feb 28.
9
An elaborate classification of SNARE proteins sheds light on the conservation of the eukaryotic endomembrane system.对SNARE蛋白的精细分类揭示了真核生物内膜系统的保守性。
Mol Biol Cell. 2007 Sep;18(9):3463-71. doi: 10.1091/mbc.e07-03-0193. Epub 2007 Jun 27.
10
Mutations in the gene encoding cystatin B in progressive myoclonus epilepsy (EPM1).进行性肌阵挛癫痫（EPM1）中胱抑素B编码基因的突变。
Science. 1996 Mar 22;271(5256):1731-4. doi: 10.1126/science.271.5256.1731.
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