CNV profiles of Chinese pediatric patients with developmental disorders



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.

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Fig. 1: The sex bias in copy-number variant (CNV) burden for patients with neurodevelopmental disorders (NDDs).
Fig. 2: Frequencies and clinical features of genomic disorders between Chinese and Western patient cohorts.
Fig. 3: Novel neurodevelopmental disorder (NDD)-related genomic disorders using de novo evidence from independent patients.

Data availability

The CNV data sets used for the study are available from the corresponding author upon request.


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This work was supported by grants from CAMS Innovation Fund for Medical Sciences (2016‐I2M‐1‐008), the Beijing Natural Science Foundation (7202019 to X. Chen), the Chinese National Nature Science Fund (31671310 to X. Chen, 81873633 to Y.S.), the Eastern Scholar Fund, the Guangxi Bagui Scholar Fund, National Key Research and Development Program (2018YFC1002501), the Major Research Plan of the Provincial Science and Technology Foundation of Guangxi (AB16380214) to Y.S., Capital Health Research and Development of Special (2020-1-4071 and 2020-2-1131), and the Innovation Project of Beijing Municipal Human Resources and Social Security Bureau to X. Chen. The authors thank all involved families who contributed their de-identified CMA data to research, and are particularly grateful for the subset who collaborated on follow-up, providing detailed clinical information. The authors thank members of the collaborating clinical laboratories for performing the microarray experiments.

Author information




Conceptualization: Y.S., X.Chen. Writing: Y.S., X.Chen, H.Y., J.F.G. Review and editing: Y.S., X.Chen, J.F.G. CMA data and collection: H.Y., S.S., J.L., J.S., R.Y., Shun Zhang. CNV curation and first-round pathogenic interpretation: J.L., S.S., R.Y. CNV second-round pathogenic interpretation H.Y., J.W., X.Chen, and Y.S. Data statistics analysis: Z.L. Western CNV literature review, the comparison between Chinese and Western cohorts for CNV frequency and referred phenotype: S.S., Z.L., H.Y. Clinical information collection: H.Y., Q.C., Z.G., Y.Zhu, X.W., L.Liu, J.Z., H.Li, H.Q., Y.Lin, H.Z., M.Y., M.M., L.Z., D.Z., H.W., H.Lv, Y.Liu, and L.Liang. CMA testing and validation: S.S., J.S., C.L., Shujie Zhang, W.Li, W.Lu, Y.Zhang, H.X., F.L., Q.W., B.X., C.G. Resources and software support and intelligent suggestion: Y.Liu and X.Cui.

Corresponding authors

Correspondence to Yiping Shen or Xiaoli Chen.

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Ethics Declaration

The study was approved by the ethics committee of the respective institutions (Capital Institute of Pediatrics, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region), which allowed us to perform aggregate analysis using de-identified clinical CMA data. Additional informed consents were obtained from the parents of some individuals to publish their detailed clinical information.

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The authors declare no competing interests.

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Yuan, H., Shangguan, S., Li, Z. et al. CNV profiles of Chinese pediatric patients with developmental disorders. Genet Med (2021).

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