Autism spectrum disorder (ASD) encompasses a spectrum of pervasive neuropsychiatric disorders characterized by deficits in social interaction, communication, unusual and repetitive behaviours. The aetiology of ASD is believed to involve complex interactions between genetic and environmental factors; it can be further classified as syndromic or nonsyndromic, according to whether it is the primary diagnosis or secondary to an existing condition where both common and rare genetic variants contribute to the development of ASD or are clearly causal. The prevalence of ASD in children is increasing with higher rates of diagnosis and an estimated one in 100 affected in the UK. Given that heritability is a major contributing factor, we aim to discuss research findings to-date in the context of a high-risk autism candidate gene, SHANK3 (SH3 and multiple ankyrin repeat domain 3), with its loss resulting in synaptic function disruption. We present a 10-year-old patient with a pathogenic de novo heterozygous c.1231delC, p.Arg411Val frameshift variant in SHANK3. He presented with severe autism, attention deficit hyperactivity disorder and pathological demand avoidance, on a background of developmental impairment and language regression. The number of genes associated with autism is ever increasing. It is a heterogeneous group of disorders with no single gene conferring pathogenesis in the majority of cases. Genetic abnormalities can be detected in ~15% of ASD and these range from copy number variants in 16p11.2 and 15q13.2q13.3 to several well-known genetic disorders including tuberous sclerosis and fragile X syndrome. Further, high confidence autism genes include but are not limited to NRXN, NLGN3, NLGN4, SHANK2 and SHANK3.

中文翻译：

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SHANK3变异体是导致11岁男孩非综合征自闭症的原因，并发表了文献综述。

自闭症谱系障碍（ASD）涵盖了一系列普遍存在的神经精神障碍，其特征是社交互动，沟通，异常和重复行为缺乏。人们认为，自闭症的病因涉及遗传和环境因素之间的复杂相互作用。根据它是主要的诊断还是继发于常见和罕见遗传变异都有助于ASD发生或显然是因果关系的现有疾病的诊断，它可以进一步分为有症状的或无症状的。儿童的ASD患病率随着诊断率的升高而增加，在英国估计有每100人中有1人受到影响。鉴于遗传力是主要的影响因素，我们旨在讨论迄今为止在高风险自闭症候选基因的研究成果，SHANK3（SH3和多个锚蛋白重复域3），其丢失导致突触功能破坏。我们介绍了一个10岁的病人，在SHANK3中具有致病性的新杂合c.1231delC，p.Arg411Val移码变体。在发育障碍和语言退化的背景下，他表现出严重的自闭症，注意缺陷多动障碍和病理需求回避。与自闭症有关的基因数量正在不断增加。在大多数情况下，它是一组异质性疾病，没有单个基因会导致发病。可以在大约15％的ASD中检测到遗传异常，其范围从16p11.2和15q13.2q13.3的拷贝数变异到几种著名的遗传疾病，包括结节性硬化症和脆性X综合征。进一步，