Division of Psychiatry, University College London.
Behavioural and Brain Sciences Unit, Institute of Child Health, London, United Kingdom.
Curr Opin Psychiatry. 2018 Nov;31(6):490-495. doi: 10.1097/YCO.0000000000000456.
Investigation for genetic causes of intellectual disability has advanced rapidly in recent years. We review the assessment of copy number variants (CNVs) and the use of next-generation sequencing based assays to identify single nucleotide variation in intellectual disability. We discuss the diagnostic yields that can be expected with the different assays. There is high co-morbidity of intellectual disability and psychiatric disorders. We review the relationship between variants which are pathogenic for intellectual disability and the risk of child and adolescent onset psychiatric disorders.
The diagnostic yields from genome wide CNV analysis and whole exome sequence analysis are high - in the region of 15 and 40%, respectively - but vary according to exact referral criteria. Many variants pathogenic for intellectual disability, notably certain recurrent CNVs, have emerged as strong risk factors for other neurodevelopmental disorders such as autism spectrum disorders, attention deficit hyperactivity disorder, and schizophrenia.
It is now conceivable that etiological variants could be identified in the majority of children presenting with intellectual disability using next-generation sequencing based assays. However, challenges remain in assessment of the pathogenicity of variants, reporting of incidental findings in children and determination of prognosis, particularly in relation to psychiatric disorders.
近年来，对智力障碍遗传原因的研究进展迅速。我们回顾了拷贝数变异（CNVs）的评估以及基于下一代测序的检测方法在识别智力障碍中单核苷酸变异中的应用。我们讨论了不同检测方法可预期的诊断效果。智力障碍和精神疾病的共病率很高。我们回顾了智力障碍致病变异与儿童和青少年期起病的精神障碍风险之间的关系。
全基因组 CNV 分析和全外显子组序列分析的诊断效果很高——分别在 15%和 40%左右——但具体取决于确切的转诊标准。许多智力障碍的致病性变异，特别是某些常见的 CNVs，已成为自闭症谱系障碍、注意缺陷多动障碍和精神分裂症等其他神经发育障碍的强风险因素。
现在可以想象，使用基于下一代测序的检测方法，大多数智力障碍儿童的病因变异都可以被识别。然而，在评估变异的致病性、报告儿童的偶然发现以及确定预后方面，仍存在挑战，特别是在与精神障碍相关的方面。
