Xuyun Hu1,2, Niu Li1, Yufei Xu1, Guoqiang Li1, Tingting Yu1, Ru-En Yao1, Lijun Fu3, Jiwen Wang4, Lei Yin5, Yong Yin6, Ying Wang7, Xingming Jin8, Xiumin Wang9, Jian Wang10, Yiping Shen11,12,13. 1. Department of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 2. Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China. 3. Department of Cardiology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 4. Department of Neurology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 5. Department of Nephrology and Rheumatology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 6. Department of Respiration, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 7. Department of Internal Medicine, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 8. Department of Child Healthcare, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 9. Department of Endocrinology and Metabolism, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 10. Department of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Labwangjian@shsmu.edu.cn. 11. Department of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. yiping.shen@childrens.harvard.edu. 12. Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China. yiping.shen@childrens.harvard.edu. 13. Division of Genetics and Genomics, Boston Children's Hospital, Boston, Massachusetts, USA. yiping.shen@childrens.harvard.edu.
Abstract
PURPOSE: To evaluate the performance of proband-only medical exome sequencing (POMES) as a cost-effective first-tier diagnostic test for pediatric patients with unselected conditions. METHODS: A total of 1,323 patients were tested by POMES, which targeted 2,742 known disease-causing genes. Clinical relevant variants were Sanger-confirmed in probands and parents. We assessed the diagnostic validity and clinical utility of POMES by means of a survey questionnaire. RESULTS: POMES, ordered by 136 physicians, identified 512 pathogenic or likely pathogenic variants associated with over 200 conditions. The overall diagnostic rate was 28.8%, ranging from 10% in neonatal intensive care unit patients to over 35% in pediatric intensive care unit patients. The test results had an impact on the management of the 45.1% of patients for whom there were positive findings. The average turnaround time was 57 days; the cost was $360/case. CONCLUSION: We adopted a relatively efficient and cost-effective approach in China for the molecular diagnosis of pediatric patients with suspected genetic conditions. While training for clinical geneticists and other specialists is lagging behind in China POMES is serving as a diagnostic equalizer for patients who do not normally receive extensive clinical evaluation and clinical diagnosis prior to testing. This Chinese experience should be applicable to other developing countries that are lacking clinical, financial, and personnel resources.
PURPOSE: To evaluate the performance of proband-only medical exome sequencing (POMES) as a cost-effective first-tier diagnostic test for pediatric patients with unselected conditions. METHODS: A total of 1,323 patients were tested by POMES, which targeted 2,742 known disease-causing genes. Clinical relevant variants were Sanger-confirmed in probands and parents. We assessed the diagnostic validity and clinical utility of POMES by means of a survey questionnaire. RESULTS: POMES, ordered by 136 physicians, identified 512 pathogenic or likely pathogenic variants associated with over 200 conditions. The overall diagnostic rate was 28.8%, ranging from 10% in neonatal intensive care unit patients to over 35% in pediatric intensive care unit patients. The test results had an impact on the management of the 45.1% of patients for whom there were positive findings. The average turnaround time was 57 days; the cost was $360/case. CONCLUSION: We adopted a relatively efficient and cost-effective approach in China for the molecular diagnosis of pediatric patients with suspected genetic conditions. While training for clinical geneticists and other specialists is lagging behind in China POMES is serving as a diagnostic equalizer for patients who do not normally receive extensive clinical evaluation and clinical diagnosis prior to testing. This Chinese experience should be applicable to other developing countries that are lacking clinical, financial, and personnel resources.
Entities:
Keywords:
China experience; clinical utility; cost-effective; proband-only; subexome sequencing
Authors: Cecelia R Miller; Kristy Lee; Ruthann B Pfau; Shalini C Reshmi; Donald J Corsmeier; Sayaka Hashimoto; Ashita Dave-Wala; Vijayakumar Jayaraman; Daniel Koboldt; Theodora Matthews; Danielle Mouhlas; Maggie Stein; Aimee McKinney; Tom Grossman; Benjamin J Kelly; Peter White; Vincent Magrini; Richard K Wilson; Elaine R Mardis; Catherine E Cottrell Journal: Cold Spring Harb Mol Case Stud Date: 2020-06-12