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Lookup NU author(s): Professor John SayerORCiD
Background and objectives Joubert syndrome is a genetically heterogeneous ciliopathy associatedwith.30 genes.The characteristics of kidney disease and genotype-phenotype correlations have not been evaluated in a largecohort at a single center.Design, setting, participants,&measurementsWeevaluated 97 individualswith Joubert syndrome at theNationalInstitutes of Health Clinical Center using abdominal ultrasonography, blood and urine chemistries, and DNAsequencing.Results Patientswere ages 0.6–36 years old (mean of 9.067.6 years old); 41were female.Mutationswere identifiedin 19 genes in 92 patients; two thirds of the mutations resided in six genes: TMEM67, C5orf42, CC2D2A, CEP290,AHI1, and KIAA0586. Kidney disease was detected in 30%, most commonly in association with the followinggenes: CEP290 (six of six),TMEM67 (11 of 22), andAHI1 (three of six).No kidney disease was identified in patientswith mutations in C5orf42 (zero of 15) or KIAA0586 (zero of six). Prenatal ultrasonography of kidneyswas normalin 72% of patients with kidney disease. Specific types of kidney disease included nephronophthisis (31%), anoverlap phenotype of autosomal recessive polycystic kidney disease/nephronophthisis (35%), unilateralmulticystic dysplastic kidney (10%), and indeterminate-type cystic kidney disease (24%). Early-onset hypertensionoccurred in 24%ofpatientswith kidneydisease.Age at ESRD(n=13) rangedfrom6 to 24 years old (mean of11.364.8 years old).Conclusions Kidney disease occurs in up to one third of patientswith Joubert syndrome,most commonly in thosewithmutations in CEP290, TMEM67, andAHI1. Patients withmutations in C5orf42 or KIAA0586 are less likely todevelop kidneydisease. Prenatal ultrasonography is a poor predictor of kidney involvement in Joubert syndrome.Unilateralmulticysticdysplastic kidney andautosomal recessive polycystic kidney disease–like enlarged kidneyswith early-onset hypertension can be part of the Joubert syndrome kidney phenotype.
Author(s): Fleming LR, Doherty DA, Parisi MA, Glass IA, Bryant J, Fischer R, Turkbey B, Choyke P, Daryanani K, Vemulapalli M, Mullikin JC, Malicdan MC, Vilboux T, Sayer JA, Gahl WA, Gunay-Aygun M
Publication type: Article
Publication status: Published
Journal: Clinical Journal of the American Society of Nephrology
Year: 2017
Volume: 12
Issue: 12
Pages: 1962-1973
Print publication date: 07/12/2017
Online publication date: 01/11/2017
Acceptance date: 18/09/2017
Date deposited: 08/01/2018
ISSN (print): 1943-8044
ISSN (electronic): 1943-8052
Publisher: American Society of Nephrology
URL: https://doi.org/10.2215/CJN.05660517
DOI: 10.2215/CJN.05660517
PubMed id: 29146704
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