@article {1490454,
	title = {Copy-number variation contributes 9\% of pathogenicity in the inherited retinal degenerations},
	journal = {Genet Med},
	volume = {22},
	number = {6},
	year = {2020},
	month = {2020 Jun},
	pages = {1079-1087},
	abstract = {PURPOSE: Current sequencing strategies can genetically solve 55-60\% of inherited retinal degeneration (IRD) cases, despite recent progress in sequencing. This can partially be attributed to elusive pathogenic variants (PVs) in known IRD genes, including copy-number variations (CNVs), which have been shown as major contributors to unsolved IRD cases. METHODS: Five hundred IRD patients were analyzed with targeted next-generation sequencing (NGS). The NGS data were used to detect CNVs with ExomeDepth and gCNV and the results were compared with CNV detection with a single-nucleotide polymorphism (SNP) array. Likely causal CNV predictions were validated by quantitative polymerase chain reaction (qPCR). RESULTS: Likely disease-causing single-nucleotide variants (SNVs) and small indels were found in 55.6\% of subjects. PVs in USH2A (11.6\%), RPGR (4\%), and EYS (4\%) were the most common. Likely causal CNVs were found in an additional 8.8\% of patients. Of the three CNV detection methods, gCNV showed the highest accuracy. Approximately 30\% of unsolved subjects had a single likely PV in a recessive IRD gene. CONCLUSION: CNV detection using NGS-based algorithms is a reliable method that greatly increases the genetic diagnostic rate of IRDs. Experimentally validating CNVs helps estimate the rate at which IRDs might be solved by a CNV plus a more elusive variant.},
	issn = {1530-0366},
	doi = {10.1038/s41436-020-0759-8},
	author = {Zampaglione, Erin and Kinde, Benyam and Place, Emily M and Navarro-Gomez, Daniel and Maher, Matthew and Jamshidi, Farzad and Nassiri, Sherwin and Mazzone, J Alex and Finn, Caitlin and Schlegel, Dana and Comander, Jason and Pierce, Eric A and Bujakowska, Kinga M}
}
