Application of whole exome sequencing in detecting copy number variants in patients with developmental delay and/or multiple congenital malformations

Abstract Overcoming the 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, in that sense, with the improvement of software and databases the whole exome sequencing can quickly become an excellent strategy in the routine diagnosis of patients with 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 due to different factors including non-genetic 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. While the copy number variants detection is possible using whole exome sequencing data, such analysis presents significant challenges and cannot yet be used to replace array in deletion or duplication identification.