Sex chromosome trisomies (SCTs) (XXX, XXY, and XYY karyotypes) are associated with an elevated risk of neurodevelopmental disorders. The range of severity of the phenotype is substantial. We considered whether this variable outcome was related to the presence of copy number variants (CNVs)—stretches of duplicated or deleted DNA. A sample of 125 children with an SCT were compared with 181 children of normal karyotype who had been given the same assessments. First, we compared the groups on measures of overall CNV burden: number of CNVs, total span of CNVs, and likely functional impact (probability of loss‐of‐function intolerance, pLI, summed over CNVs). Differences between groups were small relative to within‐group variance and not statistically significant on overall test. Next, we considered whether a measure of general neurodevelopmental impairment was predicted by pLI summed score, SCT versus comparison group, or the interaction between them. There was a substantial effect of SCT/comparison status but the pLI score was not predictive of outcomes in either group. We conclude that variable presence of CNVs is not a likely explanation for the wide phenotypic variation in children with SCTs. We discuss methodological challenges of testing whether CNVs are implicated in causing neurodevelopmental problems.

中文翻译：

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拷贝数变异负担不能预测性染色体三体性儿童神经发育表型的严重性。

性染色体三体性（SCT）（XXX，XXY和XYY核型）与神经发育障碍的风险升高相关。该表型的严重程度范围很大。我们考虑了这种可变结果是否与拷贝数变异（CNV）的存在有关-复制或缺失的DNA延伸。将125名SCT患儿的样本与181名接受同样评估的正常核型患儿进行比较。首先，我们比较了衡量CNV总体负担的组：CNV的数量，CNV的总跨度以及可能的功能影响（功能丧失不耐性的概率，pLI，与CNV的总和）。相对于组内差异，组之间的差异较小，而在整体测试中差异无统计学意义。下一个，我们考虑了是否通过pLI总分，SCT与对照组的比较，或它们之间的相互作用来预测对一般神经发育障碍的测量。SCT /比较状态有实质性影响，但pLI评分均不能预测两组的结局。我们得出结论，CNV的可变存在不是SCT患儿表型广泛变异的可能解释。我们讨论测试CNV是否与引起神经发育问题有关的方法学挑战。我们得出结论，CNV的可变存在并不是SCT患儿表型广泛变异的可能解释。我们讨论测试CNV是否与引起神经发育问题有关的方法学挑战。我们得出结论，CNV的可变存在并不是SCT患儿表型广泛变异的可能解释。我们讨论测试CNV是否与引起神经发育问题有关的方法学挑战。