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Here, we report the use of whole genome sequencing (WGS) to establish a diagnosis in a family in which individuals were affected with gout, hyperuricemia associated with reduced fractional excretion of uric acid, chronic kidney disease (CKD), and secondary hyperparathyroidism, that are consistent with familial juvenile hyperuricemic nephropathy (FJHN). However, single gene testing had not detected mutations in the uromodulin (<jats:italic>UMOD<\/jats:italic>) or renin (<jats:italic>REN<\/jats:italic>) genes, which cause approximately 30\u201390% of FJHN. WGS was therefore undertaken, and this identified a heterozygous c.226G&gt;C (p.Gly76Arg) missense variant in the paired box gene 2 (<jats:italic>PAX2<\/jats:italic>) gene, which co\u2010segregated with renal tubulopathy in the family. <jats:italic>PAX2<\/jats:italic> mutations are associated with renal coloboma syndrome (RCS), which is characterized by abnormalities in renal structure and function, and anomalies of the optic nerve. Ophthalmological examination in two adult brothers affected with hyperuricemia, gout, and CKD revealed the presence of optic disc pits, consistent with optic nerve coloboma, thereby revising the diagnosis from FJHN to RCS. Thus, our results demonstrate the utility of WGS analysis in establishing the correct diagnosis in disorders with multiple etiologies.<\/jats:p>","DOI":"10.1002\/ajmg.a.61814","type":"journal-article","created":{"date-parts":[[2020,8,10]],"date-time":"2020-08-10T06:30:54Z","timestamp":1597041054000},"page":"2521-2528","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Whole genome sequence analysis identifies a <scp>PAX2<\/scp> mutation to establish a correct diagnosis for a syndromic form of hyperuricemia"],"prefix":"10.1002","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8616-0205","authenticated-orcid":false,"given":"Mark","family":"Stevenson","sequence":"first","affiliation":[{"name":"Oxford Centre for Diabetes, Endocrinology &amp; Metabolism (OCDEM) Churchill Hospital, University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alistair T.","family":"Pagnamenta","sequence":"additional","affiliation":[{"name":"Oxford BRC, WCHG, University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Reichart","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Academic Teaching Hospital  Feldkirch Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Philpott","sequence":"additional","affiliation":[{"name":"Oxford Centre for Diabetes, Endocrinology &amp; Metabolism (OCDEM) Churchill Hospital, University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate E.","family":"Lines","sequence":"additional","affiliation":[{"name":"Oxford Centre for Diabetes, Endocrinology &amp; Metabolism (OCDEM) Churchill Hospital, University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"OxClinWGS","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline M.","family":"Gorvin","sequence":"additional","affiliation":[{"name":"Oxford Centre for Diabetes, Endocrinology &amp; Metabolism (OCDEM) Churchill Hospital, University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Lhotta","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III (Nephrology and Dialysis) Academic Teaching Hospital  Feldkirch Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny C.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Oxford BRC, WCHG, University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh V.","family":"Thakker","sequence":"additional","affiliation":[{"name":"Oxford Centre for Diabetes, Endocrinology &amp; Metabolism (OCDEM) Churchill Hospital, University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ackd.2016.11.012"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22020"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa035700"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2014.232"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000092147.83480.B5"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61343-4"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.701"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390050798"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2017.101"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0109-9"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.107"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(01)00722-9"},{"key":"e_1_2_9_14_1","first-page":"535","article-title":"PAX genes in development and disease: The role of PAX2 in urogenital tract development","volume":"46","author":"Eccles M. 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