RESEARCH ARTICLE The diagnostic yield of whole exome sequencing as a first approach in consanguineous Omani renal ciliopathy syndrome patients [version 1; peer review: 2 approved with reservations] Intisar Al Alawi 1,2 , Mohammed Al Riyami 3 , Miguel Barroso-Gil 1 , Laura Powell 1 , Eric Olinger 1 , Issa Al Salmi 3,4 , John A. Sayer 1,5,6 1 Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, Tyne and Wear, NE13BZ, UK 2 National Genetic Center, Ministry of Health, Muscat, Oman 3 Renal Medicine Department, Royal Hospital, Ministry of Health, Muscat, Oman 4 Royal Hospital, Ministry of Health, Muscat, Oman 5 Renal Services, Oman Medical Speciality Board, Newcastle upon Tyne, Tyne and Wear, NE77DN, Oman 6 Newcastle Biomedical Research Centre, NIHR, Newcastle upon Tyne, Tyne and Wear, NE45PL, UK First published: 12 Mar 2021, 10:207 https://doi.org/10.12688/f1000research.40338.1 Latest published: 07 Jul 2021, 10:207 https://doi.org/10.12688/f1000research.40338.2 v1 Abstract Background: Whole exome sequencing (WES) is becoming part of routine clinical and diagnostic practice. In the investigation of inherited cystic kidney disease and renal ciliopathy syndromes, WES has been extensively applied in research studies as well as for diagnostic utility to detect various novel genes and variants. The yield of WES critically depends on the characteristics of the patient population. Methods: In this study, we selected 8 unrelated Omani children, presenting with renal ciliopathy syndromes with a positive family history and originating from consanguineous families. We performed WES in affected children to determine the genetic cause of disease and to test the yield of this approach, coupled with homozygosity mapping, in this highly selected population. DNA library construction and WES was carried out using SureSelect Human All Exon V6 Enrichment Kit and Illumina HiSeq platform. For variants filtering and annotation Qiagen Variant Ingenuity tool was used. Nexus copy number software from BioDiscovery was used for evaluation of copy number variants and whole gene deletions. Patient and parental DNA was used to confirm mutations and the segregation of alleles using Sanger sequencing. Results: Genetic analysis identified 4 potential causative homozygous variants each confirmed by Sanger sequencing in 4 clinically relevant ciliopathy syndrome genes, (TMEM231, TMEM138, WDR19 and BBS9), Open Peer Review Reviewer Status Invited Reviewers 1 2 version 2 (revision) 07 Jul 2021 version 1 12 Mar 2021 report report Enza Maria Valente , IRCCS Mondino Foundation, Pavia, Italy University of Pavia, Pavia, Italy 1. Paraskevi Goggolidou , University of Wolverhampton, Wolverhampton, UK 2. Any reports and responses or comments on the article can be found at the end of the article. Page 1 of 13 F1000Research 2021, 10:207 Last updated: 09 JUL 2021