Pacault Mathilde, Nizon Mathilde, Pichon Olivier, Vincent Marie, Le Caignec Cédric, Isidor Bertrand
CHU Nantes, Service de Génétique Médicale, Nantes, France.
CHU Nantes, Service de Génétique Médicale, Nantes, France.
Eur J Med Genet. 2019 Dec;62(12):103586. doi: 10.1016/j.ejmg.2018.11.020. Epub 2018 Nov 22.
Autism spectrum disorders are complex neurodevelopmental syndromes characterized by phenotypic and genetic heterogeneity. Further identification of causal genes may help in better understanding the underlying mechanisms of the disorder, thus improving the patients' management. To date, abnormal synaptogenesis is thought to be one of the major underlying causes of autism spectrum disorders. Here, using oligoarray-based comparative genomic hybridization, we identified a de novo deletion at 2q37.2 locus spanning 1 Mb and encompassing AGAP1 and SH3BP4, in a boy with autism and intellectual disability. Both genes have been described as being involved in endosomal trafficking, and AGAP1 in particular has been shown to be expressed in the developing brain and to play a role in dendritic spine formation and synapse function, making it a potential causative gene to our patient's phenotype.
自闭症谱系障碍是复杂的神经发育综合征，其特征在于表型和基因异质性。进一步鉴定致病基因可能有助于更好地理解该疾病的潜在机制，从而改善对患者的管理。迄今为止，异常的突触发生被认为是自闭症谱系障碍的主要潜在原因之一。在此，我们使用基于寡核苷酸芯片的比较基因组杂交技术，在一名患有自闭症和智力残疾的男孩中，鉴定出2q37.2位点上一个1兆碱基的新发缺失，该缺失区域包含AGAP1和SH3BP4。这两个基因均已被描述为参与内体运输，特别是AGAP1已被证明在发育中的大脑中表达，并在树突棘形成和突触功能中发挥作用，使其成为导致我们患者表型的潜在致病基因。
