PT - JOURNAL ARTICLE AU - Jamie M Ellingford AU - Bradley Horn AU - Christopher Campbell AU - Gavin Arno AU - Stephanie Barton AU - Catriona Tate AU - Sanjeev Bhaskar AU - Panagiotis I Sergouniotis AU - Rachel L Taylor AU - Keren J Carss AU - Lucy F L Raymond AU - Michel Michaelides AU - Simon C Ramsden AU - Andrew R Webster AU - Graeme C M Black TI - Assessment of the incorporation of CNV surveillance into gene panel next-generation sequencing testing for inherited retinal diseases AID - 10.1136/jmedgenet-2017-104791 DP - 2018 Jan 06 TA - Journal of Medical Genetics PG - jmedgenet-2017-104791 4099 - http://jmg.bmj.com/content/early/2018/01/05/jmedgenet-2017-104791.short 4100 - http://jmg.bmj.com/content/early/2018/01/05/jmedgenet-2017-104791.full AB - Background Diagnostic use of gene panel next-generation sequencing (NGS) techniques is commonplace for individuals with inherited retinal dystrophies (IRDs), a highly genetically heterogeneous group of disorders. However, these techniques have often failed to capture the complete spectrum of genomic variation causing IRD, including CNVs. This study assessed the applicability of introducing CNV surveillance into first-tier diagnostic gene panel NGS services for IRD.Methods Three read-depth algorithms were applied to gene panel NGS data sets for 550 referred individuals, and informatics strategies used for quality assurance and CNV filtering. CNV events were confirmed and reported to referring clinicians through an accredited diagnostic laboratory.Results We confirmed the presence of 33 deletions and 11 duplications, determining these findings to contribute to the confirmed or provisional molecular diagnosis of IRD for 25 individuals. We show that at least 7% of individuals referred for diagnostic testing for IRD have a CNV within genes relevant to their clinical diagnosis, and determined a positive predictive value of 79% for the employed CNV filtering techniques.Conclusion Incorporation of CNV analysis increases diagnostic yield of gene panel NGS diagnostic tests for IRD, increases clarity in diagnostic reporting and expands the spectrum of known disease-causing mutations.