Haiming Yuan1,2, Shaofang Shangguan3, Zhengchang Li3, Jingsi Luo4, Jiasun Su4, Ruen Yao5, Shun Zhang6, Chen Liang3, Qian Chen7, Zhijie Gao7, Yanli Zhu7, Shujie Zhang4, Wei Li4, Weiliang Lu4, Yu Zhang8, Hua Xie3, Fang Liu3, Qingming Wang1,2, Yangyang Lin1,2, Liying Liu6, Xiuming Wang5,9, Liyang Liang10, Jianmin Zhong11, Haibo Li12, Haiyan Qiu13, Huifeng Zhang14, Mei Yan15, Maimaiti Mireguli15, Yanhui Liu1,2, Dan Zhang16, Hongying Wang17, Haitao Lv17, Bobo Xie4, Chunrong Gui4, Xiaodai Cui8, Liping Zou6, Jian Wang5, James F Gusella18,19, Yiping Shen20,21,22,23, Xiaoli Chen24. 1. Dongguan Maternal and Child Health Care Hospital, Dongguan, China. 2. Dongguan Institute of Reproductive and Genetic Research, Dongguan, China. 3. Department of Genetics, Capital Institute of Pediatrics, Beijing, China. 4. Genetic and Metabolic Central Laboratory, Birth Defect Prevention Research Institute, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China. 5. Department of Medical Genetics, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 6. Department of Pediatrics, Chinese PLA General Hospital, Beijing, China. 7. Department of Neurology, the affiliated hospital of Capital Institute of Pediatrics, Beijing, China. 8. Department of Lab center, Capital Institute of Pediatrics, Beijing, China. 9. Department of Endocrinology, Shanghai Children Medicine Center, Shanghai, China. 10. Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China. 11. Department of Neurology, Jiangxi Children's Hospital, Nanchang, China. 12. Central Laboratory of Birth Defects Prevention and Control, Ningbo Women & Children's Hospital, Ninbo, China. 13. Department of Pediatrics, Ningbo Women & Children's Hospital, Ninbo, China. 14. Department of Pediatrics, The Second Hospital of Hebei Medical University, Shijiazhuang, China. 15. Department of Pediatrics, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Ürümqi, China. 16. Key Laboratory of Reproductive Genetics (Ministry of Education) and Department of Reproduction, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China. 17. Department of Clinical Laboratory, Children's Hospital of Soochow University, Suzhou, Jiangsu, China. 18. Molecular Neurogenetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA. 19. Blavatnik Institute, Department of Genetics, Harvard Medical School, Boston, MA, USA. 20. Genetic and Metabolic Central Laboratory, Birth Defect Prevention Research Institute, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China. yiping.shen@childrens.harvard.edu. 21. Department of Medical Genetics, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. yiping.shen@childrens.harvard.edu. 22. Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA. yiping.shen@childrens.harvard.edu. 23. Department of Neurology, Harvard Medical School, Boston, MA, USA. yiping.shen@childrens.harvard.edu. 24. Department of Genetics, Capital Institute of Pediatrics, Beijing, China. xiaolichen@pumc.edu.cn.
Abstract
PURPOSE: To examine the overall genomic copy-number variant (CNV) landscape of Chinese pediatric patients with developmental disorders. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
PURPOSE: To examine the overall genomic copy-number variant (CNV) landscape of Chinese pediatric patients with developmental disorders. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: Shirley S W Cheng; Kelvin Y K Chan; Kelphen K P Leung; Patrick K C Au; Wai-Keung Tam; Samuel K M Li; Ho-Ming Luk; Anita S Y Kan; Brian H Y Chung; Ivan F M Lo; Mary H Y Tang Journal: Am J Med Genet C Semin Med Genet Date: 2019-03-23 Impact factor: 3.908
Authors: Francisco M De La Vega; Shimul Chowdhury; Barry Moore; Erwin Frise; Jeanette McCarthy; Edgar Javier Hernandez; Terence Wong; Kiely James; Lucia Guidugli; Pankaj B Agrawal; Casie A Genetti; Catherine A Brownstein; Alan H Beggs; Britt-Sabina Löscher; Andre Franke; Braden Boone; Shawn E Levy; Katrin Õunap; Sander Pajusalu; Matt Huentelman; Keri Ramsey; Marcus Naymik; Vinodh Narayanan; Narayanan Veeraraghavan; Paul Billings; Martin G Reese; Mark Yandell; Stephen F Kingsmore Journal: Genome Med Date: 2021-10-14 Impact factor: 11.117
Authors: Ye Cao; Ho Ming Luk; Yanyan Zhang; Matthew Hoi Kin Chau; Shuwen Xue; Shirley S W Cheng; Albert Martin Li; Josephine S C Chong; Tak Yeung Leung; Zirui Dong; Kwong Wai Choy; Ivan Fai Man Lo Journal: Front Genet Date: 2022-04-14 Impact factor: 4.772