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Keywords: Clinical testing; Copy number/structural variation; Diagnostics; Mendelian disorder; Exome sequencing

H. Wang 1; Y. Lu 1; X. Dong 1; G. Lu 2; G. Cheng 3; Y. Qian 1; Q. Ni 1; P. Zhang 1; L. Yang 1; B. Wu. 1; W. Zhou 1,3

1) Center for Molecular Medicine, Children's Hospital of Fudan University, Shanghai, Shanghai, China; 2) Pediatric intensive care unit, Children’s Hospital of Fudan University, Shanghai 201102, China; 3) Department of Neonates, Key Laboratory of Neonatal Diseases, Ministry of Health, Children’s Hospital of Fudan University, Shanghai 201102, China

Background Genome sequencing was feasible to provide genetic diagnoses in critically ill infants with rapid turn around time (TAT). Herein, to delineate the value of genetic diagnosis, we provide the results from 130 pediatric patients in the hospital in China.
Methods This study was performed with an affordable trio genome sequencing (ATGS) test. The sequencing depth of patients were 40-50 X, and of their parents were 8-10 X. Patients from PICU/NICU with complicated clinical features were enrolled from June 2018 to Dec. 2018, each with phenotypes suggesting of an underlying genetic disorder.
Results The ATGS testing identified diagnostic variants in 47.7% (62/130) individuals. The TAT was 3-5 work days and the cost was 2500$ per family. Of the sixty-two infants with diagnoses, 48 (77.4%) patients were found with pathogenic single-nucleotide variants (SNVs), 12 (19.4%) patients were detected with pathogenic copy number variations (CNVs) or structure variants (SVs), 2 (3.2%) patients were found small deletions plus pathogenic variants in another allele of autosomal recessive gene. Therapeutic strategies of 48.4% (30/62) diagnosed patients were modified, including transplantation, dietary recommendation or change of drugs, which obviously avoided morbidity and improved prognosis.
Conclusions This study provided a powerful capacity of ATGS testing in detecting of SNVs and chromosome abnormalities with fast response, higher diagnostic yield and lower cost. ATGS shows the potential to be the first tier genetic test in critically ill infants in developmental country.