title: Sequencing-based diagnostics for pediatric genetic diseases: progress and potential.
abstract: The last two decades have witnessed revolutionary changes in clinical diagnostics, fueled by the Human Genome Project and advances in high throughput, Next Generation Sequencing (NGS). We review the current state of sequencing-based pediatric diagnostics, associated challenges, and future prospects.
  
  
  
  We present an overview of genetic disease in children, review the technical aspects of Next Generation Sequencing and the strategies to make molecular diagnoses for children with genetic disease. We discuss the challenges of genomic sequencing including incomplete current knowledge of variants, lack of data about certain genomic regions, mosaicism, and the presence of regions with high homology. Expert commentary: NGS has been a transformative technology and the gap between the research and clinical communities has never been so narrow. Therapeutic interventions are emerging based on genomic findings and the applications of NGS are progressing to prenatal genetics, epigenomics and transcriptomics.
authors.affiliation: a Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine , The Children's Hospital of Philadelphia , Philadelphia , PA , USA.|b The Perelman School of Medicine , The University of Pennsylvania , Philadelphia , PA , USA.
authors.forename: Ahmad N
authors.initials: AN
authors.lastname: Abou Tayoun
authors.affiliation: a Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine , The Children's Hospital of Philadelphia , Philadelphia , PA , USA.|b The Perelman School of Medicine , The University of Pennsylvania , Philadelphia , PA , USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Krock
authors.affiliation: a Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine , The Children's Hospital of Philadelphia , Philadelphia , PA , USA.|b The Perelman School of Medicine , The University of Pennsylvania , Philadelphia , PA , USA.
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Spinner
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D030342:Genetic Diseases, Inborn / Q000175:diagnosis* / Q000235:genetics*; D015894:Genome, Human; D023281:Genomics / Q000379:methods* / Q000592:standards / Q000639:trends; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods* / Q000592:standards / Q000639:trends; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009030:Mosaicism
keywords: Genomic diagnostics; exome sequencing; genome sequencing; next generation sequencing; pediatric diagnostics; variant interpretation