大约30%的孤独症儿童属于低口语孤独症儿童，他们完全没有口语或只会使用固定短 语，或尽管会使用一些语言但语言不具有沟通功能。尽管近些年来低口语孤独症儿童逐 渐引起了研究者的关注，目前对低口语孤独症儿童的认识仍然很有限。本研究中我们利 用国际孤独症样本库Simons Simplex Collection (SSC)和本课题组建立的中国孤独症样本库 中的数据，从表型和遗传学两方面出发对低口语孤独症儿童进行研究。 SSC中，相比于有口语孤独症儿童表现出的表达性语言能力显著高于接受性语言能力， 低口语孤独症儿童尤其是其中的无口语亚组的接受性语言能力显著高于其表达性语言能 力。本课题组样本库中的中国低口语孤独症儿童表现出了与SSC中相同的表达性-接受性 语言谱。另外，随着年龄的增长，7-17周岁低口语孤独症儿童的表达性语言能力基本保持 不变，而其接受性语言能力逐渐增长。相比于同龄的有口语孤独症儿童，4-6周岁低口语 孤独症儿童表现出更多的异常感官兴趣和自伤行为，7-17周岁低口语孤独症儿童表现出更 多的异常感官兴趣、攻击非照顾者或家庭成员行为和自伤行为。但低口语孤独症儿童的 无口语亚组和有一些口语亚组之间有感官问题或攻击、自伤行为的儿童的比例往往没有 显著差异或仅有边缘性的显著差异。另外，低口语孤独症儿童的感官问题与其自伤行为 呈显著正相关。 利用基于SSC样本的遗传学数据，我们探索了低口语孤独症儿童与其他语言水平孤独 症儿童在遗传上的差异。我们发现，低口语和中等口语孤独症儿童中新发LOF (loss-offunction)突变所在基因之间的蛋白-蛋白相互作用和共表达水平显著高于预期，而高口语 孤独症儿童中新发LOF突变所在基因之间的蛋白-蛋白相互作用和共表达水平均与预期值 没有显著差异。另外，低口语和中等口语孤独症儿童中的新发LOF突变所在基因均显著富 集智力障碍相关基因，并且低口语孤独症儿童中的新发LOF突变所在基因还同时显著富集 癫痫相关基因。 本课题组为国内的低口语孤独症儿童开发了国内首款辅助沟通移动应用—小雨滴，并在10位低口语孤独症儿童中评估了小雨滴使用训练的效果。小雨滴的内置图片库包含 400多张图片和对应的语句，并将图片和语句分为了从简单需求表达到情绪表达的39类别。 依靠小雨滴丰富的个体定制功能，家长或训练者可以选择要展示的图片和语句、制作新 图片、改变页面布局和图片数目、设置图片的动态展示效果。家长或训练者可以通过 iTunes应用商店、Google Play商店或其他国内安卓应用商店来免费下载安装小雨滴。小雨 滴使用训练包含5个训练阶段，训练阶段和步骤是根据图片交换沟通系统的训练阶段和步 骤来制定的。每位孤独症儿童至少在3个训练阶段中达到了三次连续独立正确反应。在各 个训练阶段中，统计已经达到三次连续独立正确反应的儿童在此阶段的正确率，10位儿 童中的7位儿童至少在两个阶段达到50%，而2位儿童在其参加的所有训练阶段中均达到50% 以上。 本研究中我们充分利用国际孤独症样本库和本课题组的中国孤独症样本库中的表型 数据和遗传学数据，揭示了低口语孤独症儿童与其他语言水平孤独症儿童之间的差异， 并且在表型分析中我们还关注了低口语孤独症儿童的内部差异。我们发现两个样本库中 低口语孤独症儿童的表型分析结果有很高的一致性。另外，我们为国内的低口语孤独症 儿童开发了一款有丰富的内置图片库、有灵活的定制功能以及可免费获取的辅助沟通移 动应用，并证实该应用的使用训练可以提高低口语孤独症儿童表达需求的能力。

About 30% of children with Autism spectrum disorder(ASD) are minimally verbal(MV) who use a small repertoire of spoken words or fixed phrases, or use stereotyped or scripted spoken language in the noncommutative ways. Neglected for a long time, MV children with ASD are finally getting attentions in recent years. But the knowledge of this population is still limited.In this study, we explored the phenotypic and genetic aspects of MV children with ASD using data from theSimons Simplex Collection (SSC) and the sample database built by our research group. In the SSC, the receptive language skills of MV children were significantly higher than their expressive language skill while the reverse expressive-receptive language profiles was found among verbal children. The higher receptive language skills of MV children was mainly contributed by MV children with few-to-no words. In addition, theexpressive-better-thanreceptive language profile was also found among MV children in the sample database built by our research group. While the expressive language skills of7-17 year-old MV children were relatively constant, their receptive language skills increased significantly with age.Compared to verbal children of the same age, 4-6 year-old MV children showed more unusual sensory interests and self-injurious behaviors, and 7-17 year-old MV childrenshowed more unusual sensory interests, aggressive behaviors toward noncaregivers or family members, and selfinjurious behaviors. The percentage of children with sensory problems and aggressive and selfinjuriousbehaviors were not significantly or marginally significantly different between MV children with few-to-no words and MV children with some words. In addition, the sensory problems of MV children were significantly positively correlated with their self-injurious behaviors. Based on genetic data from the SSC samples, we explored the genetic differences between MV children and children with higher spoken language. We found that genes with de novo LOF(loss-of-function)mutations found in the MV and middle-level language groups have significantly higherlevels of protein interactions and coexpression between them, and genes with de novo LOF mutationsfound in the high-level language group showed expected levels of protein interactions and coexpression. In addition, genes with de novo LOF mutations found among MV children and children with middle-level language were significantly overlapped with candidate genes of intellectual disability, andgenes with de novo LOF mutations found among MV children were also significantly overlapped with candidate genes of epileptic encephalopathy. In this study, we developed an AAC mobile App, which is the first in Mainland China to our knowledge, named Yuudee (Chinese name: 小雨滴 (xiaoyudi)). We trained ten minimally verbal children with ASD to make requests using Yuudee and evaluated the effectiveness of the training. Yuudee has a built-in library of over 400 pictures with corresponding spoken phrases that are divided into 39 categories ranging from making simple requests to expressing emotions. An additional important feature of Yuudee is its customization functions that allow a parent or trainer to easily select pictures and phrases to display; create new pictures and phrases; and change the layouts and orders of the pictures to fit the personal needs of each child. Yuudee is freely available in an iOS version from the iTunes App Store and in an Android version from Google Play and domestic Chinese Android App stores. A five-phase training protocol for making requests using Yuudee was developed based on the Picture Exchange Communication System (PECS). Three consecutive unprompted successful responses were achieved in at least three of the five phases for all ten of the evaluated children. Seven children achieved at least 50% accuracy in at least two of the five phases. Two children achieved at least 50% accuracy in all of the phases in which they were trained. Our data suggest that Yuudee is a useful tool for helping minimally verbal children with ASD make requests. Inthis study, we found the phenotypic and genetic differences between MV children and verbal children with ASD using data from the SSC and the sample database built by our research group. We also found the phenotypic differences between subgroups of MV children. The phenotypic characteristics found among MV children in the two databases were largely similar. In addition, we developed a freely available AAC mobile App named Yuudee that features a large built-in picture library and a set of customization functions, and the evaluation data suggested that the use of Yuudee with our PECS-derived training procedures was effective in improving the requesting skills of minimally verbal children with ASD.