{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T17:10:05Z","timestamp":1756314605354,"version":"3.44.0"},"reference-count":16,"publisher":"BMJ","issue":"1","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Case Rep"],"accepted":{"date-parts":[[2024,12,30]]},"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>Paired box 2 (<jats:italic>PAX2<\/jats:italic>)-related disorder, also known as renal coloboma syndrome, is a variably penetrant autosomal dominant condition, associated with renal and ophthalmological abnormalities. We report a child with <jats:italic>PAX2<\/jats:italic>-related disorder who presented atypically with acute ataxia on a background of stage 3 chronic kidney disease. Extensive biochemical, radiological and gene agnostic rapid trio exome sequencing was non-diagnostic. Identification of bilateral optic disc colobomas in the proband and his father raised the suspicion of an inherited <jats:italic>PAX2<\/jats:italic>-related disorder. No causative variants were identified on a focused review of the filtered genomic data. Given the strong suspicion of an inherited monogenic disorder, whole genome trio sequencing was requested. Analysis assuming incomplete penetrance identified a paternally inherited <jats:italic>PAX2<\/jats:italic> microdeletion encompassing exon 4. This case adds to evidence of a broader <jats:italic>PAX2<\/jats:italic>-associated phenotype. It highlights the importance of a clinical genetics and mainstream interface when navigating and interpreting genetic testing.<\/jats:p>","DOI":"10.1136\/bcr-2024-263723","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T23:45:35Z","timestamp":1737503135000},"page":"e263723","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["\u2018No causative variants found\u2019: an unusual presentation of PAX2-related disorder not detected on rapid whole exome sequencing testing"],"prefix":"10.1136","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4838-888X","authenticated-orcid":false,"given":"Patricia A","family":"Wells","sequence":"first","affiliation":[{"name":"Northern Genetics Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1356-3027","authenticated-orcid":false,"given":"Anna P","family":"Basu","sequence":"additional","affiliation":[{"name":"Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK"},{"name":"Paediatric Neurology, Great North Childrens Hospital, Newcastle upon Tyne, Tyne and Wear, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7963-625X","authenticated-orcid":false,"given":"Laura M","family":"Yates","sequence":"additional","affiliation":[{"name":"Northern Genetics Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK"},{"name":"Transitional and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,1,21]]},"reference":[{"key":"2025082709422300000_18.1.e263723.1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320290318"},{"key":"2025082709422300000_18.1.e263723.2","doi-asserted-by":"publisher","DOI":"10.1093\/ckj\/sft058"},{"key":"2025082709422300000_18.1.e263723.3","doi-asserted-by":"crossref","DOI":"10.1002\/mgg3.701","article-title":"Diverse phenotypes in children with PAX2-related disorder","volume":"7","author":"Deng","year":"2019","journal-title":"Mol Genet Genomic Med"},{"key":"2025082709422300000_18.1.e263723.4","doi-asserted-by":"crossref","DOI":"10.3389\/fped.2021.765929","article-title":"PAX2 Mutation-Related Renal Hypodysplasia: Review of the Literature and Three Case Reports","volume":"9","author":"Chang","year":"2021","journal-title":"Front Pediatr"},{"key":"2025082709422300000_18.1.e263723.5","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-020-0741-y"},{"key":"2025082709422300000_18.1.e263723.6","doi-asserted-by":"crossref","DOI":"10.1186\/s12920-021-01102-x","article-title":"Phenotypic spectrum and genetics of PAX2-related disorder in the Chinese cohort","volume":"14","author":"Yang","year":"2021","journal-title":"BMC Med Genomics"},{"key":"2025082709422300000_18.1.e263723.7","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22020"},{"key":"2025082709422300000_18.1.e263723.8","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1080\/13816810.2021.2015786","article-title":"Ocular phenotype in a patient with PAX2 gene mutation-associated papillorenal syndrome","volume":"43","author":"Benador-Shen","year":"2022","journal-title":"Ophthalmic Genet"},{"key":"2025082709422300000_18.1.e263723.9","unstructured":"NHS England . The national genomic test directory. 2024. Available: https:\/\/www.england.nhs.uk\/genomics\/the-national-genomic-test-directory\/"},{"key":"2025082709422300000_18.1.e263723.10","unstructured":"Exeter Clinical Laboratory International . R14 rapid genome sequencing service. 2024. 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