{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:26:04Z","timestamp":1791300364651,"version":"4.1.0"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2017,12]]},"abstract":"\n Background and objectives<\/jats:title>\n Joubert syndrome is a genetically heterogeneous ciliopathy associated with >30 genes. The characteristics of kidney disease and genotype-phenotype correlations have not been evaluated in a large cohort at a single center.<\/jats:p>\n <\/jats:sec>\n \n Design, setting, participants, & measurements<\/jats:title>\n We evaluated 97 individuals with Joubert syndrome at the National Institutes of Health Clinical Center using abdominal ultrasonography, blood and urine chemistries, and DNA sequencing.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Patients were ages 0.6\u201336 years old (mean of 9.0\u00b17.6 years old); 41 were female. Mutations were identified in 19 genes in 92 patients; two thirds of the mutations resided in six genes:\n TMEM67<\/jats:italic>\n ,\n C5orf42<\/jats:italic>\n ,\n CC2D2A<\/jats:italic>\n ,\n CEP290<\/jats:italic>\n ,\n AHI1<\/jats:italic>\n , and\n KIAA0586<\/jats:italic>\n . Kidney disease was detected in 30%, most commonly in association with the following genes:\n CEP290<\/jats:italic>\n (six of six),\n TMEM67<\/jats:italic>\n (11 of 22), and\n AHI1<\/jats:italic>\n (three of six). No kidney disease was identified in patients with mutations in\n C5orf42<\/jats:italic>\n (zero of 15) or\n KIAA0586<\/jats:italic>\n (zero of six). Prenatal ultrasonography of kidneys was normal in 72% of patients with kidney disease. Specific types of kidney disease included nephronophthisis (31%), an overlap phenotype of autosomal recessive polycystic kidney disease\/nephronophthisis (35%), unilateral multicystic dysplastic kidney (10%), and indeterminate-type cystic kidney disease (24%). Early-onset hypertension occurred in 24% of patients with kidney disease. Age at ESRD (\n n<\/jats:italic>\n =13) ranged from 6 to 24 years old (mean of 11.3\u00b14.8 years old).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Kidney disease occurs in up to one third of patients with Joubert syndrome, most commonly in those with mutations in\n CEP290<\/jats:italic>\n ,\n TMEM67<\/jats:italic>\n , and\n AHI1<\/jats:italic>\n . Patients with mutations in\n C5orf42<\/jats:italic>\n or\n KIAA0586<\/jats:italic>\n are less likely to develop kidney disease. Prenatal ultrasonography is a poor predictor of kidney involvement in Joubert syndrome. Unilateral multicystic dysplastic kidney and autosomal recessive polycystic kidney disease\u2013like enlarged kidneys with early-onset hypertension can be part of the Joubert syndrome kidney phenotype.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.2215\/cjn.05660517","type":"journal-article","created":{"date-parts":[[2017,11,16]],"date-time":"2017-11-16T20:25:43Z","timestamp":1510863943000},"page":"1962-1973","source":"Crossref","is-referenced-by-count":69,"title":["Prospective Evaluation of Kidney Disease in Joubert Syndrome"],"prefix":"10.2215","volume":"12","author":[{"given":"Leah R.","family":"Fleming","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Doherty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa A.","family":"Parisi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian A.","family":"Glass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joy","family":"Bryant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxanne","family":"Fischer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baris","family":"Turkbey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Choyke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kailash","family":"Daryanani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghana","family":"Vemulapalli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Mullikin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"May Christine","family":"Malicdan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Vilboux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Sayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Gahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meral","family":"Gunay-Aygun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2017,11,16]]},"reference":[{"key":"B1-20230813","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1002\/ajmg.c.30225","article-title":"Liver and kidney disease in ciliopathies.","volume":"151C","author":"Gunay-Aygun","year":"2009","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"B3-20230813","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1212\/WNL.19.9.813","article-title":"Familial agenesis of the cerebellar vermis. A syndrome of episodic hyperpnea, abnormal eye movements, ataxia, and retardation.","volume":"19","author":"Joubert","year":"1969","journal-title":"Neurology"},{"key":"B4-20230813","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1177\/088307389901400605","article-title":"Molar tooth sign in Joubert syndrome: Clinical, radiologic, and pathologic significance.","volume":"14","author":"Maria","year":"1999","journal-title":"J Child Neurol"},{"key":"B6-20230813","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/S1474-4422(13)70136-4","article-title":"Joubert syndrome: Congenital cerebellar ataxia with the molar tooth.","volume":"12","author":"Romani","year":"2013","journal-title":"Lancet Neurol"},{"key":"B7-20230813","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1002\/(SICI)1096-8628(19991029)86:5<459::AID-AJMG12>3.0.CO;2-C","article-title":"Cerebello-oculo-renal syndromes including Arima, Senior-L\u00f6ken and COACH syndromes: More than just variants of Joubert syndrome.","volume":"86","author":"Satran","year":"1999","journal-title":"Am J Med Genet"},{"key":"B8-20230813","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1002\/ajmg.a.20437","article-title":"Molar tooth sign of the midbrain-hindbrain junction: Occurrence in multiple distinct syndromes.","volume":"125A","author":"Gleeson","year":"2004","journal-title":"Am J Med Genet A"},{"key":"B9-20230813","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1002\/ajmg.1320430415","article-title":"Joubert syndrome: A review.","volume":"43","author":"Saraiva","year":"1992","journal-title":"Am J Med Genet"},{"key":"B10-20230813","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1136\/jmedgenet-2015-103087","article-title":"Joubert syndrome: A model for untangling recessive disorders with extreme genetic heterogeneity.","volume":"52","author":"Bachmann-Gagescu","year":"2015","journal-title":"J Med Genet"},{"key":"B11-20230813","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s004670050394","article-title":"Lack of large, homozygous deletions of the nephronophthisis 1 region in Joubert syndrome type B. APN Study Group. Arbeitsgemeinschaft f\u00fcr P\u00e4diatrische Nephrologie.","volume":"12","author":"Hildebrandt","year":"1998","journal-title":"Pediatr Nephrol"},{"key":"B12-20230813","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1055\/s-2007-973701","article-title":"Follow-up in children with Joubert syndrome.","volume":"28","author":"Steinlin","year":"1997","journal-title":"Neuropediatrics"},{"key":"B13-20230813","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1002\/ajmg.a.31832","article-title":"Meckel syndrome in the Hutterite population is actually a Joubert-related cerebello-oculo-renal syndrome.","volume":"143A","author":"Boycott","year":"2007","journal-title":"Am J Med Genet A"},{"key":"B14-20230813","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1542\/peds.94.1.111","article-title":"Senior-Loken syndrome: Revisited.","volume":"94","author":"Warady","year":"1994","journal-title":"Pediatrics"},{"key":"B15-20230813","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/ng1786","article-title":"The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4.","volume":"38","author":"Sayer","year":"2006","journal-title":"Nat Genet"},{"key":"B16-20230813","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1007\/s00467-005-2054-y","article-title":"Identification of the first AHI1 gene mutations in nephronophthisis-associated Joubert syndrome.","volume":"21","author":"Utsch","year":"2006","journal-title":"Pediatr Nephrol"},{"key":"B17-20230813","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1136\/jmedgenet-2016-104425","article-title":"Joubert syndrome: Neuroimaging findings in 110 patients in correlation with cognitive function and genetic cause.","volume":"54","year":"2017","journal-title":"J Med Genet"},{"key":"B18-20230813","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/ki.2012.169","article-title":"Improved equations estimating GFR in children with chronic kidney disease using an immunonephelometric determination of cystatin C.","volume":"82","author":"Schwartz","year":"2012","journal-title":"Kidney Int"},{"key":"B19-20230813","doi-asserted-by":"crossref","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate.","volume":"150","author":"Levey","year":"2009","journal-title":"Ann Intern Med"},{"key":"B21-20230813","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/nature07517","article-title":"Accurate whole human genome sequencing using reversible terminator chemistry.","volume":"456","author":"Bentley","year":"2008","journal-title":"Nature"},{"key":"B22-20230813","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1681\/ASN.2008030287","article-title":"New equations to estimate GFR in children with CKD.","volume":"20","author":"Schwartz","year":"2009","journal-title":"J Am Soc Nephrol"},{"key":"B25-20230813","doi-asserted-by":"crossref","first-page":"972","DOI":"10.2215\/CJN.07141009","article-title":"Correlation of kidney function, volume and imaging findings, and PKHD1 mutations in 73 patients with autosomal recessive polycystic kidney disease.","volume":"5","author":"Gunay-Aygun","year":"2010","journal-title":"Clin J Am Soc Nephrol"},{"key":"B27-20230813","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1093\/ndt\/gfn777","article-title":"Unilateral multicystic dysplastic kidney: A meta-analysis of observational studies on the incidence, associated urinary tract malformations and the contralateral kidney.","volume":"24","author":"Schreuder","year":"2009","journal-title":"Nephrol Dial Transplant"},{"key":"B28-20230813","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1136\/jmg.2005.036608","article-title":"AHI1 mutations cause both retinal dystrophy and renal cystic disease in Joubert syndrome.","volume":"43","author":"Parisi","year":"2006","journal-title":"J Med Genet"},{"key":"B29-20230813","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.ajhg.2015.07.001","article-title":"Mutations in TBX18 cause dominant urinary tract malformations via transcriptional dysregulation of ureter development.","volume":"97","author":"Vivante","year":"2015","journal-title":"Am J Hum Genet"},{"key":"B30-20230813","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1007\/s00467-010-1454-9","article-title":"HNF1B alterations associated with congenital anomalies of the kidney and urinary tract.","volume":"25","author":"Nakayama","year":"2010","journal-title":"Pediatr Nephrol"},{"key":"B31-20230813","doi-asserted-by":"crossref","first-page":"484","DOI":"10.5414\/CN107136","article-title":"Different phenotypes of HNF1\u00df deletion mutants in familial multicystic dysplastic kidneys.","volume":"79","author":"Hasui","year":"2013","journal-title":"Clin Nephrol"},{"key":"B32-20230813","doi-asserted-by":"crossref","first-page":"3042","DOI":"10.1002\/ajmg.a.34173","article-title":"Co-occurrence of distinct ciliopathy diseases in single families suggests genetic modifiers.","volume":"155A","author":"Zaki","year":"2011","journal-title":"Am J Med Genet A"},{"key":"B33-20230813","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1002\/humu.23054","article-title":"TMEM231 Gene conversion associated with Joubert and Meckel-Gruber syndromes in the same family.","volume":"37","author":"Maglic","year":"2016","journal-title":"Hum Mutat"},{"key":"B34-20230813","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1681\/ASN.2015091029","article-title":"Risk factors for severe renal disease in bardet-biedl syndrome.","volume":"28","author":"Forsythe","year":"2017","journal-title":"J Am Soc Nephrol"},{"key":"B35-20230813","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1136\/adc.70.6.520","article-title":"Outcome of antenatally detected cystic dysplastic kidney disease.","volume":"70","author":"al-Khaldi","year":"1994","journal-title":"Arch Dis Child"},{"key":"B36-20230813","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.jpurol.2014.06.001","article-title":"The natural history of the multicystic dysplastic kidney--Is limited follow-up warranted?","volume":"10","author":"Eickmeyer","year":"2014","journal-title":"J Pediatr Urol"}],"container-title":["Clinical Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/01277230-201712000-00009","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T13:40:35Z","timestamp":1786369235000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/01277230-201712000-00009"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,16]]},"references-count":30,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2017]]}},"URL":"https:\/\/doi.org\/10.2215\/cjn.05660517","relation":{},"ISSN":["1555-9041","1555-905X"],"issn-type":[{"value":"1555-9041","type":"print"},{"value":"1555-905X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,16]]}}}