Application of custom-designed oligonucleotide array CGH in 145 patients with autistic spectrum disorders
Application of custom-designed oligonucleotide array CGH in 145 patients with autistic spectrum disorders
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DOI：
10.1038/ejhg.2012.219
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发表时间：
2013-06-01
影响因子：
5.2
通讯作者：
Stankiewicz, Pawel
中科院分区：
文献类型：
--
作者：
Wisniowiecka-Kowalnik, Barbara;Kastory-Bronowska, Monika;Stankiewicz, Pawel
自闭症谱系障碍（ASD）是一组异质性的神经发育障碍，包括儿童自闭症，非典型自闭症和Barger综合征，估计在一般人群中的患病率为1.0-2.5%。ASD具有复杂的多因素病因学，仅在10-20%的病例中识别出遗传原因。最近，拷贝数变异（CNVs）已被证明有助于超过10%的ASD病例。我们应用了定制设计的寡核苷酸阵列比较基因组杂交，外显子覆盖超过1700个基因，包括221个已知引起自闭症的基因和自闭症候选基因，在145例ASD患者的队列中。根据ICD-10标准和儿童孤独症评定量表方案将患者分为3组，包括45名有发育迟缓/智力残疾（DD/ID）的个体和69名无DD/ID的个体，以及31名不能排除DD/ID的患者。在12名患者中，我们确定了16个拷贝数变化，其中8个（5.5%）可能导致ASD。除了已知的复发性CNV，如缺失15q11.2（BP 1-BP 2）和3q13.31（包括DRD 3和ZBTB 20），以及重复15q13.3和16p13.11，我们的分析揭示了两个与ASD临床相关的新基因：ARHGAP 24（4q21.23q21.3）和SLC 16 A7（12q14.1）。我们的研究结果进一步证实了阵列CGH在ASD患者中检测CNVs的诊断重要性，并证明CNVs是ASD作为具有多种贡献基因的异质性疾病的重要原因。
Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental disorders, including childhood autism, atypical autism, and Asperger syndrome, with an estimated prevalence of 1.0-2.5% in the general population. ASDs have a complex multifactorial etiology, with genetic causes being recognized in only 10-20% of cases. Recently, copy-number variants (CNVs) have been shown to contribute to over 10% of ASD cases. We have applied a custom-designed oligonucleotide array comparative genomic hybridization with an exonic coverage of over 1700 genes, including 221 genes known to cause autism and autism candidate genes, in a cohort of 145 patients with ASDs. The patients were classified according to ICD-10 standards and the Childhood Autism Rating Scale protocol into three groups consisting of 45 individuals with and 69 individuals without developmental delay/intellectual disability (DD/ID), and 31 patients, in whom DD/ID could not be excluded. In 12 patients, we have identified 16 copy-number changes, eight (5.5%) of which likely contribute to ASDs. In addition to known recurrent CNVs such as deletions 15q11.2 (BP1-BP2) and 3q13.31 (including DRD3 and ZBTB20), and duplications 15q13.3 and 16p13.11, our analysis revealed two novel genes clinically relevant for ASDs: ARHGAP24 (4q21.23q21.3) and SLC16A7 (12q14.1). Our results further confirm the diagnostic importance of array CGH in detection of CNVs in patients with ASDs and demonstrate that CNVs are an important cause of ASDs as a heterogeneous condition with a variety of contributory genes.