{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T14:43:59Z","timestamp":1786373039681,"version":"build-2736575974"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,12]]},"abstract":"Summary<\/jats:title>\n \n Background and objectives<\/jats:title>\n In a single-center renal clinic, we have established routine mutation testing to diagnose UMOD-associated kidney disease (UAKD), an autosomal dominant disorder typically characterized by gout, hyperuricemia, and renal failure in the third to sixth decades.<\/jats:p>\n <\/jats:sec>\n \n Design, setting, participants, & measurements<\/jats:title>\n \n Four probands and their multigeneration kindreds were assessed by clinical, historical, and biochemical means. Diagnostic\n UMOD<\/jats:italic>\n sequencing was performed, and mutant uromodulin was characterized\n in vitro<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n All available affected members of the four kindreds harbored the same complex indel change in\n UMOD<\/jats:italic>\n , which was associated with almost complete absence of gout and a later onset of CKD; the youngest age at ESRD or death was 38 years (range, 38 to 68 years) compared with 3 to 70 years in other reports. Three mutation carriers (all \u226435 years) are currently asymptomatic. The indel sequence (c.278_289del TCTGCCCCGAAGinsCCGCCTCCT; p.V93_G97del\/ins AASC) results in the replacement of five amino acids, including one cysteine, by four novel residues, also including a cysteine. Uromodulin staining of the only available patient biopsy suggested disorganized intracellular trafficking with cellular accumulation. Functional characterization of the mutant isoform revealed retarded intracellular trafficking associated with endoplasmic reticulum (ER) retention and reduced secretion into cell culture media, but to a lesser extent than we observed with the previously reported C150S mutation.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n The indel mutation is associated with a relatively mild clinical UAKD phenotype, consistent with our\n in vitro<\/jats:italic>\n analysis. UAKD should be routinely considered as a causative gene for ESRD of unknown cause, especially where there is an associated family history or where biopsy reveals interstitial fibrosis.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.2215\/cjn.06820711","type":"journal-article","created":{"date-parts":[[2011,10,27]],"date-time":"2011-10-27T22:34:47Z","timestamp":1319754887000},"page":"2766-2774","source":"Crossref","is-referenced-by-count":19,"title":["Characterization of a Recurrent In-frame UMOD Indel Mutation Causing Late-onset Autosomal Dominant End-Stage Renal Failure"],"prefix":"10.2215","volume":"6","author":[{"given":"Graham D.","family":"Smith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew P.","family":"Stewart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily L.","family":"Edwards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah I.","family":"Karet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony G. W.","family":"Norden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard N.","family":"Sandford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona E.","family":"Karet Frankl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-8-20230811","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1046\/j.1523-1755.2001.00932.x","article-title":"Confirmation of a gene locus for medullary cystic kidney disease (MCKD2) on chromosome 16p12","volume":"60","author":"Hateboer","year":"2001","journal-title":"Kidney Int"},{"key":"R2-8-20230811","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1136\/jmg.39.12.882","article-title":"Mutations of the UMOD gene are responsible for medullary cystic kidney disease 2 and familial juvenile hyperuricaemic nephropathy","volume":"39","author":"Hart","year":"2002","journal-title":"J Med Genet"},{"key":"R3-8-20230811","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.ajhg.2009.07.010","article-title":"Dominant renin gene mutations associated with early-onset hyperuricemia, anemia, and chronic kidney failure","volume":"85","author":"Zivn\u00e1","year":"2009","journal-title":"Am J Hum Genet"},{"key":"R4-8-20230811","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1046\/j.1523-1755.2003.00903.x","article-title":"Atypical familial juvenile hyperuricemic nephropathy associated with a hepatocyte nuclear factor-1\u03b2 gene mutation","volume":"63","author":"Bingham","year":"2003","journal-title":"Kidney Int"},{"key":"R5-8-20230811","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s00439-010-0897-1","article-title":"Genome-wide study of familial juvenile hyperuricaemic (gouty) nephropathy (FJHN) indicates a new locus, FJHN3, linked to chromosome 2p22.1-p21","volume":"129","author":"Piret","year":"2011","journal-title":"Hum Genet"},{"key":"R6-8-20230811","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1016\/S0022-5347(05)67203-5","article-title":"Cyto-injury factors in urine: A possible mechanism for the development of interstitial cystitis","volume":"164","author":"Parsons","year":"2000","journal-title":"J Urol"},{"key":"R7-8-20230811","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/S0140-6736(80)91396-3","article-title":"Tamm-Horsfall protein or uromucoid is the normal urinary slime that traps type 1 fimbriated Escherichia coli","volume":"315","author":"Orskov","year":"1980","journal-title":"Lancet"},{"key":"R8-8-20230811","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1111\/j.1523-1755.2004.00867.x","article-title":"Tamm-Horsfall protein is a critical renal defense factor protecting against calcium oxalate crystal formation","volume":"66","author":"Mo","year":"2004","journal-title":"Kidney Int"},{"key":"R9-8-20230811","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1093\/hmg\/ddq077","article-title":"Uromodulin is expressed in renal primary cilia and UMOD mutations result in decreased ciliary uromodulin expression","volume":"19","author":"Zaucke","year":"2010","journal-title":"Hum Mol Genet"},{"key":"R10-8-20230811","doi-asserted-by":"crossref","first-page":"2938","DOI":"10.1093\/ndt\/gfl330","article-title":"Does Tamm-Horsfall protein-uric acid binding play a significant role in urate homeostasis?","volume":"21","author":"Gersch","year":"2006","journal-title":"Nephrol Dial Transplant"},{"key":"R11-8-20230811","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1111\/j.1600-0854.2006.00481.x","article-title":"Defective intracellular trafficking of uromodulin mutant isoforms","volume":"7","author":"Bernascone","year":"2006","journal-title":"Traffic"},{"key":"R12-8-20230811","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1681\/ASN.2006020158","article-title":"Membrane targeting and secretion of mutant uromodulin in familial juvenile hyperuricemic nephropathy","volume":"18","author":"Jennings","year":"2007","journal-title":"J Am Soc Nephrol"},{"key":"R13-8-20230811","doi-asserted-by":"crossref","first-page":"2963","DOI":"10.1093\/hmg\/ddp235","article-title":"Uromodulin mutations causing familial juvenile hyperuricaemic nephropathy lead to protein maturation defects and retention in the endoplasmic reticulum","volume":"18","author":"Williams","year":"2009","journal-title":"Hum Mol Genet"},{"key":"R14-8-20230811","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1681\/ASN.2009070725","article-title":"Uromodulin levels associate with a common UMOD variant and risk for Incident CKD","volume":"21","author":"K\u00f6ttgen","year":"2010","journal-title":"J Am Soc Nephrol"},{"key":"R15-8-20230811","doi-asserted-by":"crossref","first-page":"3369","DOI":"10.1093\/hmg\/ddg353","article-title":"Allelism of MCKD, FJHN and GCKD caused by impairment of uromodulin export dynamics","volume":"12","author":"Rampoldi","year":"2003","journal-title":"Hum Mol Genet"},{"key":"R18-8-20230811","doi-asserted-by":"crossref","first-page":"2998","DOI":"10.1093\/hmg\/ddq205","article-title":"A transgenic mouse model for uromodulin-associated kidney diseases shows specific tubulo-interstitial damage, urinary concentrating defect and renal failure","volume":"19","author":"Bernascone","year":"2010","journal-title":"Hum Mol Genet"},{"key":"R19-8-20230811","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1046\/j.1523-1755.2003.00269.x","article-title":"Mutations of the uromodulin gene in MCKD type 2 patients cluster in exon 4, which encodes three EGF-like domains","volume":"64","author":"Wolf","year":"2003","journal-title":"Kidney Int"},{"key":"R20-8-20230811","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1038\/sj.ki.5002089","article-title":"The uromodulin C744G mutation causes MCKD2 and FJHN in children and adults and may be due to a possible founder effect","volume":"71","author":"Wolf","year":"2007","journal-title":"Kidney Int"},{"key":"R21-8-20230811","doi-asserted-by":"crossref","first-page":"2883","DOI":"10.1097\/01.ASN.0000092147.83480.B5","article-title":"A cluster of mutations in the UMOD gene causes familial juvenile hyperuricemic nephropathy with abnormal expression of uromodulin","volume":"14","author":"Dahan","year":"2003","journal-title":"J Am Soc Nephrol"},{"key":"R22-8-20230811","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1053\/j.ajkd.2005.04.003","article-title":"A novel pattern of mutation in uromodulin disorders: Autosomal dominant medullary cystic kidney disease type 2, familial juvenile hyperuricemic nephropathy, and autosomal dominant glomerulocystic kidney disease","volume":"46","author":"Lens","year":"2005","journal-title":"Am J Kid Dis"},{"key":"R23-8-20230811","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1210\/jc.2002-021973","article-title":"Uromodulin mutations cause familial juvenile hyperuricemic nephropathy","volume":"88","author":"Turner","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"R24-8-20230811","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1074\/jbc.M110.149880","article-title":"Tamm-Horsfall glycoprotein interacts with renal outer medullary potassium channel ROMK2 and regulates its function","volume":"286","author":"Renigunta","year":"2011","journal-title":"J Biol Chem"},{"key":"R25-8-20230811","doi-asserted-by":"crossref","first-page":"F1405","DOI":"10.1152\/ajprenal.00522.2009","article-title":"Mutation of the Na+-K+-2Cl- cotransporter NKCC2 in mice is associated with severe polyuria and a urea-selective concentrating defect without hyperreninemia","volume":"298","author":"Kemter","year":"2010","journal-title":"Am J Physiol Renal Physiol"},{"key":"R26-8-20230811","doi-asserted-by":"crossref","first-page":"F1391","DOI":"10.1152\/ajprenal.00261.2009","article-title":"Novel missense mutation of uromodulin in mice causes renal dysfunction with alterations in urea handling, energy, and bone metabolism","volume":"297","author":"Kemter","year":"2009","journal-title":"Am J Physiol Renal Physiol"},{"key":"R27-8-20230811","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1093\/rheumatology\/33.10.932","article-title":"Polynesian women are also at risk for hyperuricaemia and gout because of a genetic defect in renal urate handling","volume":"33","author":"Simmonds","year":"1994","journal-title":"Br J Rheumatol"},{"key":"R28-8-20230811","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s004670050466","article-title":"Presymptomatic detection of familial juvenile hyperuricaemic nephropathy in children","volume":"12","author":"McBride","year":"1998","journal-title":"Pediatr Nephrol"},{"key":"R29-8-20230811","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1093\/qjmed\/95.9.597","article-title":"Early treatment with allopurinol in familial juvenile hyerpuricaemic nephropathy (FJHN) ameliorates the long-term progression of renal disease","volume":"95","author":"Fairbanks","year":"2002","journal-title":"Quart J Med"},{"key":"R30-8-20230811","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1080\/15257770600891028","article-title":"Familial juvenile hyperuricaemic nephropathy is not such a rare genetic metabolic purine disease in Britain","volume":"25","author":"Simmonds","year":"2006","journal-title":"Nucleoside Nucleotide Nucleic Acids"}],"container-title":["Clinical Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/01277230-201112000-00008","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T13:41:27Z","timestamp":1786369287000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/01277230-201112000-00008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,12]]},"references-count":28,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2011]]}},"URL":"https:\/\/doi.org\/10.2215\/cjn.06820711","relation":{},"ISSN":["1555-9041"],"issn-type":[{"value":"1555-9041","type":"print"}],"subject":[],"published":{"date-parts":[[2011,12]]}}}