{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:06:43Z","timestamp":1772168803578,"version":"3.50.1"},"update-to":[{"DOI":"10.12688\/f1000research.109628.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T00:00:00Z","timestamp":1680220800000}}],"reference-count":25,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T00:00:00Z","timestamp":1680220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004185","name":"Northern Counties Kidney Research Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004185","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000291","name":"Kidney Research UK","doi-asserted-by":"publisher","award":["Paed_RP_001_20180925"],"award-info":[{"award-number":["Paed_RP_001_20180925"]}],"id":[{"id":"10.13039\/501100000291","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns7:p>\n                    <ns7:bold>Background.<\/ns7:bold>\n                    Joubert syndrome (JS) is a rare autosomal recessive ciliopathy with an estimated prevalence of 1 in 100,000. JS is characterized by hyperpnoea, hypotonia, ataxia, developmental delay and various neuropathological abnormalities in the brain including cerebellar hypoplasia and cerebellar vermis aplasia. JS can also have variable multi-organ involvement, including the retina, kidneys, liver, and musculoskeletal system.\n                  <\/ns7:p>\n                  <ns7:p>\n                    <ns7:bold>Methods and Results<\/ns7:bold>\n                    . Here we report a clinical description of two-year-old girl presenting with breathing difficulties, hyperechoic kidneys with loss of corticomedullary differentiation. Brain magnetic resonance imaging revealed the typical molar tooth sign consistent with a clinical diagnosis of JS and retinal examination showed severe retinal dystrophy leading to blindness. Molecular genetic analysis using whole exome sequencing and Sanger sequence confirmation demonstrated a homozygous mutation (c.5493delA, p.(A1832fs*19) in\n                    <ns7:italic>CEP290<\/ns7:italic>\n                    which segregated from either parent and was consistent with the multisystem ciliopathy phenotype. This precise variant has been described previously in 2 families from the Kosovar-Albanian region suggesting this allele is a recurrent mutation in this population.\n                  <\/ns7:p>\n                  <ns7:p>\n                    <ns7:bold>Conclusions.<\/ns7:bold>\n                    Mutations in\n                    <ns7:italic>CEP290<\/ns7:italic>\n                    lead to multisystem ciliopathy syndromes and molecular genetic diagnostics of such cases allows precise diagnosis, screening of at risk relatives and appropriate management.\n                  <\/ns7:p>","DOI":"10.12688\/f1000research.109628.2","type":"journal-article","created":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T07:35:06Z","timestamp":1680248106000},"page":"388","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case Report: Identification of likely recurrent CEP290 mutation in a child with Joubert syndrome and cerebello-retinal-renal features."],"prefix":"10.12688","volume":"11","author":[{"given":"Lidvana","family":"Spahiu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1881-3782","authenticated-orcid":false,"given":"John A","family":"Sayer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emir","family":"Behluli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1672-3054","authenticated-orcid":false,"given":"Thomas","family":"Liehr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4807-2938","authenticated-orcid":false,"given":"Gazmend","family":"Temaj","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2023,3,31]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"229-249","DOI":"10.1002\/ajmg.a.61399","article-title":"Healthcare recommendations for Joubert syndrome.","volume":"182","author":"R Bachmann-Gagescu","year":"2020","journal-title":"Am J Med Genet 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Lange, School of Biomolecular and Biomedical Science, University College Dublin, Dublin, 14 Dec 2022, version 1, 1 approved, 1 approved with reservations","URL":"https:\/\/f1000research.com\/articles\/11-388\/v1#referee-response-156994","order":1,"name":"referee-response-156994","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>John Sayer<\/b>; \n<i>Posted: 15 Mar 2023<\/i>; \n<i>I appreciate that the authors include a table which highlights the spectrum of clinical phenotypes associated with this specific CEP290 variant. It is intriguing that previous reports of individuals that were homozygous for this allele were diagnosed with perinatal lethal Meckel Syndrome while the homozygous patient in this case study is has Joubert Syndrome. It would be worthwhile to add a sentence in the discussion to speculate on why this might be. Thank you. We have added a section on genotype phenotype correlation in CEP290.  I have some minor recommendations that would help with clarity:<\/i>  \n<i>\u201cBlood from the patient and his healthy parents\u201d&nbsp; should be her\/their.<\/i> \n<b>Corrected<\/b> &nbsp; \n<i>\u201cno clear signs of foramina magnum obstruction and a typical \u201cmolar tooth sign\u201d This should be reworded because I interpreted this as no MTS was observed (even though it is clearly shown in Figure 1C)<\/i> \n<b>&nbsp;Reworded<\/b> &nbsp; \n<i>In Table 1 It would be more clear if the Clinical Phenotype of COR001 was listed as Joubert Syndrome since COR is a subset of Joubert.<\/i> \n<b>Corrected<\/b> &nbsp; \n<i>I believe the clinical phenotype of G001347 in Table 1 should be retinal dystrophy not LCA.<\/i> \n<b>Corrected<\/b>","URL":"https:\/\/f1000research.com\/articles\/11-388\/v2#referee-comment-9466","order":2,"name":"referee-comment-9466","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"JS is funded by Kidney Research United Kingdom (Paed_RP_001_20180925) 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":3,"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"}]}}