Optical Genome Mapping: Different Types of Hidden SV's in Families with Inherited Retinal Diseases

Optical genome mapping: hidden structural variants in families with inherited retinal diseases Kornelia Neveling1,3, Zeinab Fadaie1,2, Suzanne de Bruijn1,2, Tuomo Mantere1, Ronny Derks1, Lonneke Haer-Wigman1, Amber den Ouden1, Michael Kwint1, Luke O'Gorman1, Dyon Valkenburg2,4, Carel B. Hoyng2,4, Christian Gilissen1,5, Lisenka E.L.M. Vissers1, Marcel Nelen1, Frans P.M. Cremers1,2, Susanne Roosing1,2, Alexander Hoischen1,3

1 Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.

2 Donders Institute for Brain, Cognition and Behavior, Nijmegen, The Netherlands

3 Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands

4 Department of Ophthalmology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands

5 Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands

6 Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands

The lack of molecular diagnoses in rare genetic diseases can be explained by limitations of current standard genomic technologies. Upcoming long-read techniques have complementary strengths to overcome these limitations, with a particular strength in identifying structural variants (SVs). By using optical genome mapping (Bionano Genomics) and long-read HiFi genome sequencing (Pacific Biosciences), we aimed to identify the pathogenic variant in families with molecularly unsolved inherited retinal diseases. Here, we will show a family with the X-linked progressive eye disease Choroideremia, a patient with Usher syndrome (syndromic blindness and deafness) and a patient with Senior Løken syndrome (syndromic kidney disease and eye disease). All three cases had been unsolved for many years. Optical genome mapping finally helped us to identify the different pathogenic structural vari