Comparative genomic hybridisation as a first option in genetic diagnosis: 1000 cases and a cost–benefit analysis

Comparison of the diagnostic yield of aCGH and genome-wide sequencing across different neurodevelopmental disorders

“…For aCGH we found a substantially lower diagnostic rate, overall (5.6%) and per phenotype category, than the 15–20% previously reported 10 – 12 , 25 , 26 . These differences might be attributed to multiple factors such as the criteria used for patient selection, being our cohort characterized by a high clinical heterogeneity where the genetic contribution to the phenotype is expected to vary widely; the sample size studied; the timing of the study and therefore, the knowledge about the CNVs; and the variant classification criteria used which has evolved over time with the increasing knowledge about population genomics; and the CMA methods used in other studies and their resolution.…”

“…In this study, we used a 60 K aCGH, the smallest of all commercially available arrays, what might have resulted in the lower diagnostic yield observed. Arrays with higher probe densities generally lead to an increase in the detection yield that is often accompanied by an associated increase in the number of VUS that are detected 26 . However, as most arrays used clinically, the 60 K aCGH has probes concentrated in clinically relevant genes, covering over 245 recognized genetic syndromes and over 980 gene regions of functional significance in human development, which allows for detection of smaller CNVs within disease-associated regions while minimizing the number of VUS.…”