Figure 1

Clinical copy number variation analysis algorithm. Whole genome or exome copy number variation (CNV) analysis is an accepted first-line screening tool for the evaluation of patients with complex clinical presentations, and also intellectual disability (ID), autism spectrum disorder (ASD) or multiple congenital anomalies (MCA). If negative, whole exome/clinical exome analysis is now clinically available for subsequent analysis. CNVs detected by array-based comparative genomic hybridization (aCGH) or SNP-based microarray (SNP-array) may lead to a diagnosis or point to a coexisting mutation in the affected gene(s) in autosomal recessive (AR) traits. Targeted exonic CNV analysis can similarly be applied to identify deletions in genes with a heterozygous mutation detected by DNA sequencing. The emergence of whole genome DNA sequence analysis on a clinical basis will allow for integrated whole exome CNV/whole exome sequence analysis in the near future. ARMLPA, multiplex ligation-dependent probe amplification; NGS, next-generation high-throughput DNA sequencing; qPCR, quantitative PCR.