The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683 Nicosia, Cyprus.
Biomed Res Int. 2013;2013:843027. doi: 10.1155/2013/843027. Epub 2013 Oct 24.
Autism spectrum disorders (ASDs) comprise a distinct entity of neurodevelopmental disorders with a strong genetic component. Despite the identification of several candidate genes and causative genomic copy number variations (CNVs), the majority of ASD cases still remain unresolved. We have applied microarray-based comparative genomic hybridization (array-CGH) using Agilent 400K custom array in the first Cyprus population screening for identification of ASD-associated CNVs. A cohort of 50 ASD patients (G1), their parents (G2), 50 ethnically matched normal controls (G3), and 80 normal individuals having children with various developmental and neurological conditions (G4) were tested. As a result, 14 patients were found to carry 20 potentially causative aberrations, two of which were de novo. Comparison of the four population groups revealed an increased rate of rare disease-associated variants in normal parents of children with autism. The above data provided additional evidence, supporting the complexity of ASD aetiology in comparison to other developmental disorders involving cognitive impairment. Furthermore, we have demonstrated the rationale of a more targeted approach combining accurate clinical description with high-resolution population-oriented genomic screening for defining the role of CNVs in autism and identifying meaningful associations on the molecular level.
自闭症谱系障碍（ASD）是一种具有强烈遗传成分的神经发育障碍的独特实体。尽管已经确定了一些候选基因和致病基因组拷贝数变异（CNVs），但大多数 ASD 病例仍未得到解决。我们应用了基于微阵列的比较基因组杂交（array-CGH），使用 Agilent 400K 定制阵列，对塞浦路斯的首个 ASD 相关 CNVs 人群筛查进行了鉴定。一个包括 50 名 ASD 患者（G1）、他们的父母（G2）、50 名具有不同发育和神经条件的正常儿童的父母（G3）以及 80 名正常个体（G4）的队列接受了测试。结果发现 14 名患者携带了 20 种潜在致病的异常，其中两种是新生的。对四个群体的比较显示，自闭症儿童的正常父母中罕见疾病相关变异的发生率增加。上述数据提供了额外的证据，支持 ASD 病因的复杂性与其他涉及认知障碍的发育障碍相比。此外，我们已经证明了一种更具针对性的方法的合理性，该方法将准确的临床描述与针对人口的高分辨率基因组筛查相结合，以确定 CNVs 在自闭症中的作用，并在分子水平上确定有意义的关联。
