Analysis Of Whole Exome Sequencing In 572 Children With Mendelian Disease

Objective:To analyze the diagnostic yields of whole-exome sequencing(WES)in Mendelian disorders among pediatric patients of different ethnic backgrounds in Xinjiang.And preliminaries to explore the clinical diagnostic value of WES.Methods: We retrospectively analyzed the WES results of 572 consecutive patients clinically suspected for Mendelian diseases who were admitted to the pediatric center of the First Affiliated Hospital of Xinjiang Medical University,China,between January 2016 and June 2020.The clinical information,the motives for testing,the diagnostic yield of WES,the molecular findings,and the effect on management strategy were analyzed.All tests were performed at the same accredited commercial laboratory and were re-checked and evaluated by the physician in charge.Results: The overall positive diagnostic yield was42.3%(242/572),the diagnostic yields were higher for Uyghur children(46.5%)than for Han children(36.2%),for patients from consanguineous families(70%)than for patients from non-consanguineous families(40.8%),and for patients with greater clinical complexity(85.7%)than for patients with lower clinical complexity.The medicine management of 147 patients(61.0%)was affected,while 215 patients(89.2%)had changed their clinical or diet management.Conclusion: WES is practical for clinical diagnosis of children with MD in Xinjiang.Inbreeding was one of the strongest predictors of positive WES tests.