Diagnosis of genetic disorders in childhood with next-generation sequencing

Incorporating next-generation sequencing (NGS) technology to diagnostics enables to identify a vast repertoire of genetic disorders in a single measurement. Currently, targeted gene panels and whole-exome sequencing (WES) are the most prevalent methods in clinical use due to the smaller cost of analysis and manageable amount of data compared to whole-genome sequencing (WGS). We aim to review the applicability of NGS-based technologies in the diagnosis of early-onset genetic disorders. We summarize genes associated with early-onset diseases including inborn errors of metabolism, oncological indications and pediatric genetic disorders. There are several technical and clinical issues that currently limit the everyday diagnostic application of NGS. The principal challenge lies in the interpretation of rare genetic variants and in the correct assignment of variant pathogenicity.