Clinical And Genetic Factors Analysis Of Neurodevelopmental Disorders

Background: Children neurodevelopmental disorders(NDDs)is a chronic developmental brain dysfunction diseases,caused by a variety of genetic or acquired causes,including global developmental disabilities/intellectual disabilities,autism spectrum disorders,epilepsy and attention deficit hyperactivity disorder and so on,which seriously affect children’s physical and mental health,and bring heavy economic and mental burden to the family and society.The clinical manifestations of these diseases are overlapping,maybe causing by similar molecular mechanisms.Through researched and combined with the findings of other centers around the world in this field,they deepen our understanding of the disease,while they will make us to clear pathogenesis of NDDs,identifying biomarkers for early detection,and directions for guiding patient treatment,genetic advice and birth guidance.Methods: We collect patients with NDDs who meet the inclusion criteria at the Children’s Hospital affiliated to Chongqing Medical University from september 2018 to 2021.The clinical data from probands and family members were collected.With the informed consent of family members,the peripheral blood of the probands and some family members was obtained for karyotype analysis,Whole exome sequencing and copy number variations.Then the clinical manifestations and genetic results of the probands and family members are summarized and analyzed.Results: The clinical manifestations of the children with NDDs in this study are varied.This study mainly studies those children with global developmental disabilities/intellectual disabilities,and part of that accompanied with abnormal facial shape,autism spectrum disorder,ataxia,sleep disorder and so on.In our study,children with special faces can increased the positive rate in Whole exome sequencing.In this study,genetic testing was divided into two parts.In one part,chromosome karyotype analysis in 92 out of 853 cases with NDDs were abnormal,abnomal MECP2 gene was found in 24 out of 128 patients with NDDs,AS/PWS was detected in 99 out of 400 patients with NDDs,which test were performed at the clinical molecular center of our hosipital.In the other part,210 cases were identified the molecular etiology by WES in third party gene company in the 337 patients with NDDs.And in the 210 patients,69 patients with CNVs and 141 patients with gene mutations in127 genes;the CNVs located at those chromosomes excepting chromosome13,chromosome 20,chromosome 21 and chromosome Y.Those variants affect nervous system development by influencing conserved proteins in some physiological pathways.Conclusion:Genetic factors are important pathogenesis in neurodevelopmental disorders,including chromosomal abnormalities,copy number variations and genetic abnormalities.Karyotype analysis of 853 cases with NDDs was carried out by molecular center of our hospital,and the positive rate was 10.79%.We applied Whole exome sequencing(WES)in 337 cases with NDDs,a total molecular diagnostic rate of the individual is 62.31%,including 20.47% in CNVs.Autosomal dominant inheritance were common in single gene mutations in 127 genes which influence protein synthesis,transportion,synapse,epigenetic regulation or mitochondrial respiratory chain complexes.NDDs seriously affect the physical and mental health of children,and strengthening and paying attention to the understanding of NDDs is conducive to early detection,early diagnosis and early intervention,and provides a basis for genetic inquiry and healthy birth.