BACKGROUND Variants disruptive to CHD8 (which codes for the protein CHD8 [chromodomain-helicase-DNA-binding protein 8]) are among the most common mutations revealed by exome sequencing in autism spectrum disorder (ASD). Recent work has indicated that CHD8 plays a role in the regulation of other ASD-risk genes. However, it is unclear whether a possible shared genetic ontology extends to the phenotype. METHODS This study (N = 143; 42.7% female participants) investigated clinical and behavioral features of individuals ascertained for the presence of a known disruptive ASD-risk mutation that is 1) CHD8 (CHD8 group) (n = 15), 2) a gene targeted by CHD8 (target group) (n = 22), or 3) a gene without confirmed evidence of being targeted by CHD8 (other gene group) (n = 106). RESULTS Results indicated shared features between the CHD8 and target groups that included less severe adaptive deficits in communication skills, similar functional language, more social motivation challenges in those with ASD, larger head circumference, higher weight, and lower seizure prevalence relative to the other gene group. CONCLUSIONS These similarities suggest broader genetic ontology accounts for aspects of phenotypic heterogeneity. Improved understanding of the relationships between related disruptive gene events may lead us to improved understanding of shared mechanisms and lead to more focused treatments for individuals with known genetic mutations.

中文翻译：

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CHD8或其保守靶基因突变携带者的临床表型

背景 破坏 CHD8（编码蛋白质 CHD8 [染色质结构域解旋酶 -DNA 结合蛋白 8]）的变异是自闭症谱系障碍 (ASD) 外显子组测序揭示的最常见突变之一。最近的研究表明，CHD8 在其他 ASD 风险基因的调节中发挥着作用。然而，尚不清楚可能的共享遗传本体是否扩展到表型。方法 本研究（N = 143；42.7% 女性参与者）调查了个体的临床和行为特征，确定是否存在已知的破坏性 ASD 风险突变，即 1) CHD8（CHD8 组）(n = 15)，2) a CHD8（目标组）靶向的基因（n = 22），或 3）没有确凿证据表明 CHD8（其他基因组）靶向的基因（n = 106）。结果结果表明，CHD8 和目标群体之间存在共同特征，包括沟通技巧方面不太严重的适应性缺陷、相似的功能性语言、自闭症谱系障碍患者更多的社交动机挑战、相对于其他基因而言，头围更大、体重更高以及癫痫发作率更低团体。结论 这些相似性表明更广泛的遗传本体论可以解释表型异质性的各个方面。对相关破坏性基因事件之间关系的更好理解可能会让我们更好地理解共享机制，并为具有已知基因突变的个体提供更有针对性的治疗。