Sequencing-based diagnostics for pediatric genetic diseases: progress and potential

Expert Rev Mol Diagn. 2016 Sep;16(9):987-99. doi: 10.1080/14737159.2016.1209411. Epub 2016 Aug 17.


Introduction: 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.

Areas covered: 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.

Keywords: Genomic diagnostics; exome sequencing; genome sequencing; next generation sequencing; pediatric diagnostics; variant interpretation.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Female
  • Genetic Diseases, Inborn / diagnosis*
  • Genetic Diseases, Inborn / genetics*
  • Genome, Human*
  • Genomics / methods*
  • Genomics / standards
  • Genomics / trends
  • High-Throughput Nucleotide Sequencing / methods*
  • High-Throughput Nucleotide Sequencing / standards
  • High-Throughput Nucleotide Sequencing / trends
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mosaicism