A Retrospective Study Of Trios Whole-Exome Sequencing In The Diagnosis Of Children With Suspected Mendelian Genetic Diseases

Objective The purpose of this study was to investigate the clinical diagnostic value of family whole exome sequencing（TriosWES）technology in children with suspected Mendelian genetic diseases,to analyze the detection rate and diagnostic positive rate of TriosWES technology,and its application in different systems and phenotypic diseases.diagnostic performance.Methods This study selected 199 children with suspected Mendelian genetic diseases and their families who were admitted to the Hangzhou First People’s Hospital affiliated to Zhejiang University School of Medicine from January 2019 to December 2021.Human phenotype ontology was used in this study.The（HPO）term summarizes and analyzes the clinical phenotype,diagnosis and genetic diagnosis results of children,initially explores the overall diagnostic performance of TriosWES and the distribution of causative diseases.Furthermore,diagnostic performance of different system diseases and phenotypes was evaluated in this study.Results（1）199 children and their families were tested by TriosWES in this study,including 118 male children（118/199,59.30%）and 81 female children（81/199,40.70%）.Maximum age of these children is 17 years old,the minimum age is 3 days,and the average age is（4.1 8+5.72）years old.126 cases（126/199,63.32%）of children with positive reports of variant genes were detected,of which 89 cases（89/199,44.72%）received a definite molecular diagnosis,and the remaining 73 cases（73/199,36.68%）)were tested negative.（2）In this study,81 children（81/199,40.70%）had nervous system abnormalities,26 children（26/199,13.07%）had cardiovascular system abnormalities,and urogenital system abnormalities.There were 19 cases（19/199,9.55%）of the children with abnormal blood or hematopoietic system,and 14 cases（14/199,7.04%）of them with abnormal blood or hematopoietic system.The main clinical manifestations of abnormal nervous system diseases were convulsions,growth retardation,tetany,mental retardation and abnormal EEG,among which 46 were male and 35 were female,with an average age of 3.22 years old.Positive rate of diagnosis in children with abnormal nervous system was 66.67%（54/81）.89 children with definitive diagnosis also included some rare diseases,such as hyperestrogenic syndrome,Klinefelter syndrome,Rett syndrome.congenital central hypoventilation syndrome,glycogen storage syndrome,hepatolenticular degeneration Wait and so on.Conclusion TriosWES technology has high diagnostic value in children with suspected Mendelian genetic diseases,especially when used in children with neurological abnormalities,which can effectively assist clinicians in diagnosis and genetic counseling.