Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
Am J Med Genet B Neuropsychiatr Genet. 2020 Jul;183(5):268-276. doi: 10.1002/ajmg.b.32785. Epub 2020 May 6.
Autism spectrum disorder (ASD) is a relatively common childhood onset neurodevelopmental disorder with a complex genetic etiology. While progress has been made in identifying the de novo mutational landscape of ASD, the genetic factors that underpin the ASD's tendency to run in families are not well understood. In this study, nine extended pedigrees each with three or more individuals with ASD, and others with a lesser autism phenotype, were phenotyped and genotyped in an attempt to identify heritable copy number variants (CNVs). Although these families have previously generated linkage signals, no rare CNV segregated with these signals in any family. A small number of clinically relevant CNVs were identified. Only one CNV was identified that segregated with ASD phenotype; namely, a duplication overlapping DLGAP2 in three male offspring each with an ASD diagnosis. This gene encodes a synaptic scaffolding protein, part of a group of proteins known to be pathologically implicated in ASD. On the whole, however, the heritable nature of ASD in the families studied remains poorly understood.
自闭症谱系障碍（ASD）是一种较为常见的儿童期起病的神经发育障碍，具有复杂的遗传病因。虽然在识别 ASD 的新生突变景观方面已经取得了进展，但自闭症谱系障碍在家族中倾向于遗传的遗传因素尚不清楚。在这项研究中，对 9 个扩展的家系进行了表型和基因型分析，每个家系有 3 个或更多的 ASD 患者和其他具有较轻自闭症表型的个体，试图识别可遗传的拷贝数变异（CNVs）。尽管这些家系先前已经产生了连锁信号，但在任何一个家系中，都没有罕见的 CNV 与这些信号分离。确定了少数具有临床意义的 CNVs。只有一个 CNV 与 ASD 表型分离；即，在三个男性后代中重叠 DLGAP2 的重复，每个后代都被诊断为 ASD。该基因编码一种突触支架蛋白，是一组已知与 ASD 病理相关的蛋白。然而，总的来说，在所研究的家系中，自闭症谱系障碍的可遗传性仍知之甚少。
