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Lookup NU author(s): Professor John SayerORCiD
This is the authors' accepted manuscript of an article that has been published in its final definitive form by American Society of Nephrology, 2017.
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© 2017 by the American Society of Nephrology. Background and objectives 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. Design, setting, participants, & measurements 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. Results Patients were ages 0.6–36 years old (mean of 9.0±7.6 years old); 41 were female. Mutations were identified in 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 following genes: CEP290 (six of six), TMEM67 (11 of 22), and AHI1 (three of six). No kidney disease was identified in patients with mutations in C5orf42 (zero of 15) or KIAA0586 (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=13) ranged from 6 to 24 years old (mean of 11.3±4.8 years old). Conclusions Kidney disease occurs in up to one third of patients with Joubert syndrome, most commonly in those with mutations in CEP290, TMEM67, andAHI1. Patients with mutations in C5orf42 or KIAA0586 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–like enlarged kidneys with 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: 30/11/2017
Acceptance date: 18/09/2017
Date deposited: 27/02/2018
ISSN (print): 1555-9041
ISSN (electronic): 1555-905X
Publisher: American Society of Nephrology
URL: https://doi.org/10.2215/CJN.05660517
DOI: 10.2215/CJN.05660517
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