Dongguan Maternal and Child Health Care Hospital, Dongguan, China.
Dongguan Institute of Reproductive and Genetic Research, Dongguan, China.
Genet Med. 2021 Apr;23(4):669-678. doi: 10.1038/s41436-020-01048-y. Epub 2021 Jan 5.
To examine the overall genomic copy-number variant (CNV) landscape of Chinese pediatric patients with developmental disorders.
De-identified chromosomal microarray (CMA) data from 10,026 pediatric patients with developmental disorders were collected for re-evaluating the pathogenic CNV (pCNV) yields of different medical conditions and for comparing the frequency and phenotypic variability of genomic disorders between the Chinese and Western patient populations.
The overall yield of pCNVs in the Chinese pediatric patient cohort was 21.37%, with variable yields for different disorders. Yields of pCNVs were positively associated with phenotypic complexity and intellectual disability/developmental delay (ID/DD) comorbidity for most disorders. The genomic burden and pCNV yield in neurodevelopmental disorders supported a female protective effect. However, the stratification analysis revealed that it was seen only in nonsyndromic ID/DD, not in nonsyndromic autism spectrum disorders or seizure. Furthermore, 15 known genomic disorders showed significantly different frequencies in Chinese and Western patient cohorts, and profiles of referred clinical features for 15 known genomic disorders were also significantly different in the two cohorts.
We defined the pCNV yields and profiles of the Chinese pediatric patients with different medical conditions and uncovered differences in the frequency and phenotypic diversity of genomic disorders between Chinese and Western patients.
研究中国儿科发育障碍患者的全基因组拷贝数变异（CNV）图谱。
收集了 10026 名儿科发育障碍患者的去识别染色体微阵列（CMA）数据，用于重新评估不同疾病的致病性 CNV（pCNV）发生率，并比较中西方患者群体中基因组疾病的频率和表型变异性。
中国儿科患者队列中 pCNV 的总体发生率为 21.37%，不同疾病的发生率不同。对于大多数疾病，pCNV 的发生率与表型复杂性和智力障碍/发育迟缓（ID/DD）合并症呈正相关。神经发育障碍的基因组负担和 pCNV 发生率支持女性保护效应。然而，分层分析表明，这种效应仅见于非综合征性 ID/DD，而不是非综合征性自闭症谱系障碍或癫痫。此外，15 种已知的基因组疾病在中西方患者群体中的频率有显著差异，15 种已知基因组疾病的推荐临床特征图谱在两个群体中也有显著差异。
我们定义了不同医疗条件下中国儿科患者的 pCNV 发生率和特征，并揭示了中西方患者基因组疾病的频率和表型多样性存在差异。
