biostudies-literature00440Pfundt REuropean Research CouncilDutch Research Council (NWO)667-675https://www.ebi.ac.uk/biostudies/studies/S-EPMC5460076biostudies-literatureUnknown19(6)<h4>Purpose</h4>Copy-number variation is a common source of genomic variation and an important genetic cause of disease. Microarray-based analysis of copy-number variants (CNVs) has become a first-tier diagnostic test for patients with neurodevelopmental disorders, with a diagnostic yield of 10-20%. However, for most other genetic disorders, the role of CNVs is less clear and most diagnostic genetic studies are generally limited to the study of single-nucleotide variants (SNVs) and other small variants. With the introduction of exome and genome sequencing, it is now possible to detect both SNVs and CNVs using an exome- or genome-wide approach with a single test.<h4>Methods</h4>We performed exome-based read-depth CNV screening on data from 2,603 patients affected by a range of genetic disorders for which exome sequencing was performed in a diagnostic setting.<h4>Results</h4>In total, 123 clinically relevant CNVs ranging in size from 727 bp to 15.3 Mb were detected, which resulted in 51 conclusive diagnoses and an overall increase in diagnostic yield of ~2% (ranging from 0 to -5.8% per disorder).<h4>Conclusions</h4>This study shows that CNVs play an important role in a broad range of genetic disorders and that detection via exome-based CNV profiling results in an increase in the diagnostic yield without additional testing, bringing us closer to single-test genomics.Genet Med advance online publication 27 October 2016.Genetics in medicine : official journal of the American College of Medical GeneticsDetection of clinically relevant copy-number variants by exome sequencing in a large cohort of genetic disorders.PMC5460076281964016.166.015Yntema HGSimons AStegmann APAStevens SJCDel Rosario MMensenkamp ARPfundt RKwint MPWieskamp NLugtenberg DRinne TVissers LELMJanssen IMRodenburg RJTde Leeuw NScheffer HVeltman JAGilissen CHehir-Kwa JYNelen MRKamsteeg EJ44falseDetection of clinically relevant copy-number variants by exome sequencing in a large cohort of genetic disorders.<h4>Purpose</h4>Copy-number variation is a common source of genomic variation and an important genetic cause of disease. Microarray-based analysis of copy-number variants (CNVs) has become a first-tier diagnostic test for patients with neurodevelopmental disorders, with a diagnostic yield of 10-20%. However, for most other genetic disorders, the role of CNVs is less clear and most diagnostic genetic studies are generally limited to the study of single-nucleotide variants (SNVs) and other small variants. With the introduction of exome and genome sequencing, it is now possible to detect both SNVs and CNVs using an exome- or genome-wide approach with a single test.<h4>Methods</h4>We performed exome-based read-depth CNV screening on data from 2,603 patients affected by a range of genetic disorders for which exome sequencing was performed in a diagnostic setting.<h4>Results</h4>In total, 123 clinically relevant CNVs ranging in size from 727 bp to 15.3 Mb were detected, which resulted in 51 conclusive diagnoses and an overall increase in diagnostic yield of ~2% (ranging from 0 to -5.8% per disorder).<h4>Conclusions</h4>This study shows that CNVs play an important role in a broad range of genetic disorders and that detection via exome-based CNV profiling results in an increase in the diagnostic yield without additional testing, bringing us closer to single-test genomics.Genet Med advance online publication 27 October 2016.2017-01-01T00:00:00Z2017 Jun2024-11-15T11:11:08.659Z2019-03-27T02:46:55ZS-EPMC54600762857451310.1038/gim.2016.163