Application of Whole-Exome Sequencing in Detecting Copy Number Variants in Patients with Developmental Delay and/or Multiple Congenital Malformations

J Mol Diagn. 2020 Aug;22(8):1041-1049. doi: 10.1016/j.jmoldx.2020.05.007. Epub 2020 Jun 1.


Overcoming challenges for the unambiguous detection of copy number variations is essential to broaden our understanding of the role of genomic variants in the clinical phenotype. With the improvement of software and databases, whole-exome sequencing quickly can become an excellent strategy in the routine diagnosis of patients with a developmental delay and/or multiple congenital malformations. However, even after a detailed analysis of pathogenic single-nucleotide variants and indels in known disease genes, using whole-exome sequencing, some patients with suspected syndromic conditions are left without a conclusive diagnosis. These negative results could be the result of different factors including nongenetic etiologies, lack of knowledge about the genes that cause different disease phenotypes, or, in some cases, a deletion or duplication of genomic information not routinely detectable by whole-exome sequencing variant calling. Although copy number variant detection is possible using whole-exome sequencing data, such analysis presents significant challenges and cannot yet be used to replace chromosomal arrays for identification of deletions or duplications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / blood
  • Abnormalities, Multiple / diagnosis*
  • Abnormalities, Multiple / genetics*
  • DNA Copy Number Variations*
  • Databases, Genetic
  • Developmental Disabilities / blood
  • Developmental Disabilities / diagnosis*
  • Developmental Disabilities / genetics*
  • Exome
  • Exons
  • Humans
  • INDEL Mutation
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Software
  • Whole Exome Sequencing / methods*