BACKGROUND Intellectual disability (ID) is a heterogeneous neurodevelopmental disorder with a complex genetic underpinning in its etiology. Chromosome microarray (CMA) is recommended as the first-tier diagnostic test for ID due to high detection rate of copy number variation (CNV). METHODS To identify an appropriate clinical detection scheme for ID in Han Chinese patients, whole genome low-coverage sequencing was performed as the first-tier diagnostic test, and medical exome sequencing (MES) as the second-tier diagnostic test for patients with negative results of CNVs. RESULTS A total of 19 pathogenic CNVs in 16/95(16.84%) ID patients and 10 pathogenic single-nucleotide variations (SNVs), including 6 novel mutations in 8/95(8.42%) ID patients were identified on whom no pathogenic CNVs were discovered. The detection rate of CNVs in ID with multiple congenital anomalies (MCA) subgroup was significantly higher than ID with autism spectrum disorders and other IDs subgroups. And the single-nucleotide variations showed a higher occurrence rate in the other IDs subgroup. CONCLUSIONS There were differences in the diagnostic yields of different variation types among the three ID subgroups. Our findings provided a new perspective on appropriate clinical detection scheme in different ID subgroups based on statistically significant differences among the three ID subgroups. The application of whole genome low-coverage sequencing as the first-tier diagnostic test for ID with MCA subgroup and MES as the first-tier diagnostic test for other ID subgroup was considered as an efficient clinical detection scheme.

中文翻译：

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智力障碍的诊断结果：结合了全基因组低覆盖率测序和医学外显子组测序。

背景技术智力障碍（ID）是一种异质性神经发育障碍，其病因具有复杂的遗传基础。染色体微阵列（CMA）被推荐作为ID的第一级诊断测试，因为其拷贝数变异（CNV）的检测率很高。方法为确定汉族人群ID的临床检测方案，对结果阴性的全基因组低覆盖率测序作为第一级诊断测试，对医学外显子组测序（MES）作为第二级诊断测试CNV。结果在16/95（16.84％）ID患者中共鉴定出19个病原性CNV，在10/95（8.42％）ID患者中鉴定出10个病原性单核苷酸变异（SNV），其中6个新突变未发现病原性CNV。发现。具有多个先天性异常（MCA）子组的ID中CNV的检出率显着高于具有自闭症谱系障碍和其他ID子组的ID。单核苷酸变异在其他IDs亚组中显示出更高的发生率。结论在三个ID亚组中，不同变异类型的诊断结果存在差异。我们的发现基于三个ID子组之间的统计学显着差异，为不同ID子组中的适当临床检测方案提供了新的视角。将全基因组低覆盖率测序作为MCA亚组ID的一级诊断测试和MES作为其他ID亚组的ID一级诊断测试的应用被认为是一种有效的临床检测方案。