Social Responsiveness Scale-aided analysis of the clinical impact of copy number variations in autism.
Social Responsiveness Scale-aided analysis of the clinical impact of copy number variations in autism.
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DOI：
10.1007/s10048-011-0297-2
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发表时间：
2011-11
期刊：
影响因子：
2.2
通讯作者：
Poot M
中科院分区：
文献类型：
--
作者：
van Daalen E;Kemner C;Verbeek NE;van der Zwaag B;Dijkhuizen T;Rump P;Houben R;van 't Slot R;de Jonge MV;Staal WG;Beemer FA;Vorstman JA;Burbach JP;van Amstel HK;Hochstenbach R;Brilstra EH;Poot M
最近基于芯片的研究在自闭症谱系障碍 (ASD) 患者中检测到了大量的拷贝数变异 (CNV)。由于 CNV 也发生在健康个体中，因此它们对患者表型的贡献在很大程度上仍不清楚。在一组有 ASD 症状的儿童中，使用 ADOS-G 和 ADI-R 对指标患者进行诊断，并对指标患者、父母双方以及所有可用的兄弟姐妹进行社会反应量表 (SRS)。使用 SNP 阵列鉴定 CNV，并通过 FISH 或阵列 CGH 进行确认。为了评估 CNV 的临床意义，我们分析了三个有多个受影响儿童的家庭（多重）和六个有一个受影响儿童的家庭（单一），其中至少一个孩子携带带有脑转录基因的 CNV。含有参与先前与 ASD 相关的通路的基因的 CNV，例如磷酸肌醇信号通路 (PIK3CA、GIRDIN)、基于接触素的细胞通讯网络 (CNTN6) 和小头磷脂 (MCPH1)，被发现不与 ASD 表型共分离。在一个家族中，CNTN5 的缺失与疾病共同分离。这表明大多数 CNV 本身可能不足以引起 ASD，但仍然可能通过与遗传（遗传）突变或非遗传因素的加性或上位相互作用而促成表型。我们的研究将全基因组 CNV 分析的范围扩展到散发患者的从头 CNV 之外，并可能有助于发现复杂精神疾病的全基因组筛查研究中缺失的遗传性。
Recent array-based studies have detected a wealth of copy number variations (CNVs) in patients with autism spectrum disorders (ASD). Since CNVs also occur in healthy individuals, their contributions to the patient’s phenotype remain largely unclear. In a cohort of children with symptoms of ASD, diagnosis of the index patient using ADOS-G and ADI-R was performed, and the Social Responsiveness Scale (SRS) was administered to the index patients, both parents, and all available siblings. CNVs were identified using SNP arrays and confirmed by FISH or array CGH. To evaluate the clinical significance of CNVs, we analyzed three families with multiple affected children (multiplex) and six families with a single affected child (simplex) in which at least one child carried a CNV with a brain-transcribed gene. CNVs containing genes that participate in pathways previously implicated in ASD, such as the phosphoinositol signaling pathway (PIK3CA, GIRDIN), contactin-based networks of cell communication (CNTN6), and microcephalin (MCPH1) were found not to co-segregate with ASD phenotypes. In one family, a loss of CNTN5 co-segregated with disease. This indicates that most CNVs may by themselves not be sufficient to cause ASD, but still may contribute to the phenotype by additive or epistatic interactions with inherited (transmitted) mutations or non-genetic factors. Our study extends the scope of genome-wide CNV profiling beyond de novo CNVs in sporadic patients and may aid in uncovering missing heritability in genome-wide screening studies of complex psychiatric disorders.
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影响因子：
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Scherer, Stephen W.
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