Introduction: Since the implementation of molecular karyotyping in diagnostics of neurodevelopmental disorders(NDDs), the understanding of the genetic causes of these diseases has significantly improved.However, with the introduction of the Next Generation Sequencing (NGS), the setting of the genotype-phenotype correlations has become even more straightforward. By determining causative mutationsin individual genes, it enabled us to understand the role of individual genes in the aetiology of thedisease, and significantly increased the diagnostic yield for genetic diagnostic of NDDs in Slovenianchildren. Methods: In this study, we present a small series of paediatric patients with various NDDs where molecularkaryotyping as the first-tier diagnostic test in our laboratory did not show the presence ofmicrodeletion or microduplication, which could explain the patients' clinical picture. By using thepanel sequencing of 4813 genes (TruSight One Illumina Kit) and focusing on phenotype drivenanalysis, we were able to identify the genetic origin of the disorder (pathogenic Single NucleotideVariant – pSNV) in 29% (N 13/45) of screened patients. In 24% (N 11/45) of patients, a SNV classifiedas variant of unknown significance (VOUS) has been determined within the disease-associated genes. Discussion: Although a small series of Slovenian paediatric patients were analysed using target NGS sequencing,our study illustrates the high usability of this method in diagnostic of NDDs. With phenotype-genotypedriven analysis, we were able to identify rare and clinically poorly defined syndromes in previouslyundiagnosed patients. Among them, disorders such as Kabuki and Noonan syndrome, Menkesdisease, mutations in IQSEC2 gene causing the Rett-like phenotype etc. were identified. A highpercent of pSNV are also partly due to the selection of suitable patients for NGS testing based on theirgood clinical characterization. Our study confirmed a high efficiency of NGS in diagnostic of NDDs andenabled the diagnosis of rarely described cases which will be presented.
F.22 Improvement to existing health/diagnostic methods/procedures
COBISS.SI-ID: 6813503