Copy number variations in cryptogenic cerebral palsy
Copy number variations in cryptogenic cerebral palsy
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DOI：
10.1212/wnl.0000000000001494
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发表时间：
2015-04-21
期刊：
影响因子：
9.9
通讯作者：
Levy-Lahad, Ephrat
中科院分区：
文献类型：
--
作者：
Segel, Reeval;Ben-Pazi, Hilla;Levy-Lahad, Ephrat
目的：探讨病因不明的脑性瘫痪(CP)患儿中拷贝数变异(CNV)的发生率和特点。方法：52例患儿(年龄10.5~7.8岁，粗大运动功能分类系统评分2.8~1.3)，自幼有锥体和/或锥体外系非进行性体征，病因不明。有获得性病因证据的个人被排除在外。参与者在基因组测试之前接受了神经学和临床遗传学检查。利用Affymetrix平台进行染色体微阵列分析以检测CNV。确认的CNV被分类为致病的、可能的致病的、可能的良性或良性的。结果：52例受试者中有25例(48%)检出39例CNV。16名参与者(31%)有临床意义的CNV：10例致病，6例可能致病，其中7例以前与运动障碍无关。9名参与者可能患有良性CNV。临床上有意义的CNV更多地是从头开始(12/16；P<；0.001)，包括有一级或二级亲属患有严重神经疾病的8人中的5人。畸形特征和非运动合并症在有临床意义的CNV患者中更为常见(P<；0.05)。结论：CNV最常见于隐源性CP患者。我们建议对病因不明的慢性阻塞性肺病患者进行CNV检测。
Objective:To determine the prevalence and characteristics of copy number variations (CNVs) in children with cerebral palsy (CP) of unknown etiology, comprising approximately 20% of the CP population.Methods:Fifty-two participants (age 10.5 7.8 years; Gross Motor Function Classification System scale 2.8 1.3) with nonprogressive pyramidal and/or extrapyramidal signs since infancy and no identified etiology were enrolled. Individuals with evidence of acquired causes were excluded. Participants underwent neurologic and clinical genetic examinations before the genomic testing. Chromosomal microarray analysis to detect CNVs was performed using the Affymetrix platform. CNVs identified were classified as pathogenic, likely pathogenic, likely benign, or benign. Only pathogenic and likely pathogenic CNVs were defined as clinically significant.Results:Thirty-nine CNVs were found in 25 of 52 participants (48%). Sixteen participants (31%) had clinically significant CNVs: 10 pathogenic and 6 likely pathogenic, of which 7 were not previously associated with motor disability. Nine participants had likely benign CNVs. Clinically significant CNVs were more frequently de novo (12/16; p < 0.001) including in 5 of 8 individuals who had a first- or second-degree relative with a major neurologic disorder. Dysmorphic features and nonmotor comorbidities were more prevalent in individuals with clinically significant CNVs (p < 0.05 for both).Conclusion:CNVs, most frequently de novo, are common in individuals with cryptogenic CP. We recommend CNV testing in individuals with CP of unknown etiology.