Genetic analysis of neurodevelopmental disorders in children.

Purpose: To explore the genetic cause of children with unidentified etiology of neurodevelopmental disorders, thus providing references for the diagnosis, treatment and genetic counseling. Design and methods: Children with neurodevelopmental disorders but unidentified etiology in the Child Healthcare Department, Children's Hospital of Nanjing Medical University from November 2018 to December 2021 were retrospectively analyzed. A total of 2 ml of peripheral venous blood was collected from the child and their parents for the whole exome sequencing (WES) and copy number variation (CNV) detection. Male children were subjected to fragile X syndrome testing to determine the genetic mutations. For those with positive results, Sanger sequencing was performed to explore the mutations in the gene sites and pedigrees. Results: A total of 488 (33.5%) pathogenic variations were detected among 1,457 global developmental/intellectual disabilities (GDD/ID) children, including 362 (24.9%) cases of monogenic mutations, and 111 (7.6%) cases of chromosomal microdeletions or microduplications. There were 15/780 (1.92%) male children with fragile X syndrome. Single point mutations were detected in 277/362 (76.5%) and 85/362 (23.5%) male and female GDD/ID children, respectively, including 295 (81.5%) cases of missense mutations, 32 (8.8%) cases of frameshift mutations, 5 (2.2%) cases of non-sense mutations and 30 (8.3%) cases of splice site mutations. In addition, there were 166 (45.8%) cases of autosomal inheritance and 196 (54.2%) cases of X-linked inheritance. The X chromosome abnormalities were mostly observed in 362 GDD/ID children with monogenic mutations, including 15 cases of the Conclusion: The incidence of genetic abnormalities remains high in NDD children. Abundant novel mutations are responsible for GDD/ID in children, and can be used as references in the diagnosis of neurogenetic diseases.