Department of Psychiatry, Research Laboratory "Vulnerability to Psychotic Disorders LR 05 ES 10", Monastir University Hospital, Monastir, Tunisia.
Faculty of Pharmacy, University of Monastir, Monastir, Tunisia.
Mol Genet Genomic Med. 2022 Aug;10(8):e1939. doi: 10.1002/mgg3.1939. Epub 2022 Jun 27.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with strong genetic underpinnings. Microarray-based comparative genomic hybridization (aCGH) technology has been proposed as a first-level test in the genetic diagnosis of ASD and of neurodevelopmental disorders in general.
We performed aCGH on 98 Tunisian children (83 boys and 15 girls) diagnosed with ASD according to DSM-IV criteria.
"Pathogenic" or "likely pathogenic" copy number variants (CNVs) were detected in 11 (11.2%) patients, CNVs of "uncertain clinical significance" in 26 (26.5%), "likely benign" or "benign" CNVs were found in 37 (37.8%) and 24 (24.5%) patients, respectively. Gene set enrichment analysis involving genes spanning rare "pathogenic," "likely pathogenic," or "uncertain clinical significance" CNVs, as well as SFARI database "autism genes" in common CNVs, detected eight neuronal Gene Ontology classes among the top 10 most significant, including synapse, neuron differentiation, synaptic signaling, neurogenesis, and others. Similar results were obtained performing g: Profiler analysis. Neither transcriptional regulation nor immune pathways reached significance.
aCGH confirms its sizable diagnostic yield in a novel sample of autistic children from North Africa. Recruitment of additional families is under way, to verify whether genetic contributions to ASD in the Tunisian population, differently from other ethnic groups, may involve primarily neuronal genes, more than transcriptional regulation and immune-related pathways.
自闭症谱系障碍（ASD）是一种具有强烈遗传基础的神经发育障碍。基于微阵列的比较基因组杂交（aCGH）技术已被提议作为 ASD 及一般神经发育障碍的基因诊断的一级检测方法。
我们对 98 名根据 DSM-IV 标准诊断为 ASD 的突尼斯儿童（83 名男孩和 15 名女孩）进行了 aCGH 检测。
在 11 名（11.2%）患者中检测到“致病性”或“可能致病性”拷贝数变异（CNVs），26 名（26.5%）患者中检测到“可能具有临床意义”的 CNVs，37 名（37.8%）和 24 名（24.5%）患者中分别发现“可能良性”或“良性”CNVs。涉及跨越罕见“致病性”、“可能致病性”或“不确定临床意义”CNVs 的基因以及常见 CNVs 中 SFARI 数据库“自闭症基因”的基因集富集分析，在排名前 10 的最显著基因本体论类别中检测到 8 个神经元类别，包括突触、神经元分化、突触信号、神经发生等。使用 g:Profiler 分析也得到了类似的结果。转录调控和免疫途径均未达到显著水平。
aCGH 证实了其在来自北非的新型自闭症儿童样本中的较大诊断产量。正在招募更多的家庭，以验证突尼斯人群中 ASD 的遗传贡献是否与其他种族群体不同，可能主要涉及神经元基因，而不是转录调控和免疫相关途径。
