Using Whole Exome Sequencing to Identify Genetic Causes of Neurodevelopmental Disorders in a Cohort of 11 Patients: A Single Center Experience

Neurodevelopmental disorders (NDDs) represent a heterogeneous group of diseases with a variety of clinical presentations related to different genetic, epigenetic, and environmental etiologies. Numerous pathogenic variants have been identified by comprehensive genetic approaches such as next-generation sequencing and chromosomal microarray analyses. This study included eleven pediatric patients with NDDs who were referred to our Molecular Medicine (MM) unit for further diagnostic workup. Whole exome sequencing (WES) was performed, and data were analyzed as part of a contracted service with the National Genomic Center and iBioScience LTD. Likely pathogenic single nucleotide variants in genes <i>DDX3X</i> c.869C>A, p.S290* and <i>CNOT1</i> c.920delG, p.G307Afs*32 in two patients, and pathogenic copy number variants in the 16p11.2 (16:29,690,418-30,200,285)x3 and 16p12.1-p11.2 (16:27,078,317-29,001,333)x3 regions in a third patient with NDDs were identified. In a fourth patient, the c.6839A>G, p.Gln2280Arg variant of uncertain significance was found in the <i>NIPBL</i> gene. Altogether, our study has revealed four novel variants in genes previously linked to NDDs. Identification of genetic causes of NDDs not only promotes establishing a more precise diagnosis and improves our understanding of disease pathogenesis but may also provide better means for developing preventive measures for the recurrence of this serious condition.