{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T21:12:34Z","timestamp":1789679554816,"version":"4.0.1"},"update-to":[{"DOI":"10.12688\/f1000research.40338.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,7,7]],"date-time":"2021-07-07T00:00:00Z","timestamp":1625616000000}}],"reference-count":35,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2021,7,7]],"date-time":"2021-07-07T00:00:00Z","timestamp":1625616000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Research Council Grant, Oman","award":["ORG\/HSS\/14\/ 015"],"award-info":[{"award-number":["ORG\/HSS\/14\/ 015"]}]},{"name":"The Northern Counties Kidney Research Fund, UK"},{"name":"Medical Research Council Discovery Medicine North Training Partnership"},{"name":"Early Postdoc Mobility Stipendium of the Swiss National Science Foundation","award":["P2ZHP3_195181"],"award-info":[{"award-number":["P2ZHP3_195181"]}]},{"DOI":"10.13039\/501100000291","name":"Kidney Research UK","doi-asserted-by":"crossref","award":["ST_001_20171120, Paed_RP_001_20180925"],"award-info":[{"award-number":["ST_001_20171120, Paed_RP_001_20180925"]}],"id":[{"id":"10.13039\/501100000291","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Ministry of Health, Oman"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>\n                    <ns3:bold>Background:<\/ns3:bold>\n                    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.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Methods:<\/ns3:bold>\n                    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.\n                  <\/ns3:p>\n                  <ns3:p>\n                    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\n                    <ns3:bold\/>\n                    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.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Results:<\/ns3:bold>\n                    Genetic analysis identified 4 potential causative homozygous variants each confirmed by Sanger sequencing in 4 clinically relevant ciliopathy syndrome genes, (\n                    <ns3:italic>TMEM231<\/ns3:italic>\n                    ,\n                    <ns3:italic>TMEM138<\/ns3:italic>\n                    ,\n                    <ns3:italic>WDR19<\/ns3:italic>\n                    and\n                    <ns3:italic>BBS9<\/ns3:italic>\n                    ), leading to an overall diagnostic yield of 50%.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Conclusions:<\/ns3:bold>\n                    WES coupled with homozygosity mapping provided a diagnostic yield of 50% in this selected population. This genetic approach needs to be embedded into clinical practise to allow confirmation of clinical diagnosis, to inform genetic screening as well as family planning decisions. Half of the patients remain without diagnosis highlighting the technical and interpretational hurdles that need to be overcome in the future.\n                  <\/ns3:p>","DOI":"10.12688\/f1000research.40338.2","type":"journal-article","created":{"date-parts":[[2021,7,7]],"date-time":"2021-07-07T13:32:05Z","timestamp":1625664725000},"page":"207","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["The diagnostic yield of whole exome sequencing as a first approach in consanguineous Omani renal ciliopathy syndrome patients"],"prefix":"10.12688","volume":"10","author":[{"given":"Intisar","family":"Al Alawi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3698-5609","authenticated-orcid":false,"given":"Mohammed","family":"Al Riyami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Barroso-Gil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Powell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1178-7980","authenticated-orcid":false,"given":"Eric","family":"Olinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3443-5972","authenticated-orcid":false,"given":"Issa","family":"Al Salmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1881-3782","authenticated-orcid":false,"given":"John 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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.58306.r89232, Enza Maria Valente, Neurogenetics Research Center, IRCCS Mondino Foundation, Pavia, Italy, 12 Jul 2021, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/10-207\/v2#referee-response-89232","order":0,"name":"referee-response-89232","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.58306.r89233, Paraskevi Goggolidou, Department of Biomedical Science and Physiology, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, UK, 19 Jul 2021, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/10-207\/v2#referee-response-89233","order":1,"name":"referee-response-89233","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"Al Alawi was supported by the Ministry of Health and The Research Council Grant (ORG\/HSS\/14\/ 015), Oman. MB-G is funded by Kidney Research UK (ST_001_20171120) and the Northern Counties Kidney Research Fund. LP is funded by the Medical Research Council Discovery Medicine North Training Partnership. EO is supported by an Early Postdoc Mobility Stipendium of the Swiss National Science Foundation (P2ZHP3_195181) and Kidney Research UK (Paed_RP_001_20180925). JAS is funded by Kidney Research UK and the Northern Counties Kidney Research Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}