高通量测序技术在智力障碍/全面发育迟缓中的临床应用

Clinical application of next generation sequencing in molecular diagnosis of intellectual disability/global developmental delay

智力障碍是一组常见的神经发育障碍性疾病,基因型和表型的异质性都很高,对其的明确诊断越来越依赖全基因组范围内的分子诊断。基于高通量测序(NGS)的panel测序,全外显组测序甚至全基因组测序在智障的分子诊断上都有很好的应用,推荐家系全外显组测序,特别是家系全外作为首选检测方法。针对智障的的NGS数据分析以及重分析对诊断有临床意义,可以可靠检测出基因组内的小尺度突变及拷贝数变异。因此有可能会成为下一个推荐的智障分子诊断技术。

Intellectual disability(ID)is a group of neurodevelopmental disorders with high heterogeneous in both genotypes and phenotypes and its definitive diagnosis is increasingly dependent ongenome-wide molecular diagnostics.Based on next generation sequencing(NGS),panel sequencing,whole exome sequencing(WES)and even whole genome sequencing are well applied to the molecular diagnosis of ID.Based on these,we recommend WES,especially trio-WES as the preferred detection method.NGS data analysis and reanalysis for ID have clinical significance for diagnosis,and can detect small scale variation and copy number variation in the genome reliably.Therefore,it has the potential to become the next recommended molecular diagnostic toolfor ID.