Prospective evaluation of kidney disease in joubert syndrome

Leah R. Fleming, Daniel A. Doherty, Melissa A. Parisi, Ian A. Glass, Joy Bryant, Roxanne Fischer, Baris Turkbey, Peter Choyke, Kailash Daryanani, Meghana Vemulapalli, James C. Mullikin, May Christine Malicdan, Thierry Vilboux, John A. Sayer, William A. Gahl, Meral Gunay-Aygun

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1962-1973
Number of pages12
JournalClinical Journal of the American Society of Nephrology
Issue number12
StatePublished - Dec 7 2017


  • Abnormalities, multiple
  • Cerebellum
  • Ciliopathies
  • Ciliopathy
  • Cystic kidney
  • Eye abnormalities
  • Genetic association studies
  • Genetic renal disease
  • Hypertension
  • Joubert syndrome 1
  • Kidney
  • Kidney diseases, cystic
  • Kidney failure, chronic
  • Multicystic dysplastic kidney
  • Mutation
  • Nephronophthisis
  • Phenotype
  • Polycystic kidney disease
  • Polycystic kidney, autosomal recessive
  • Pregnancy
  • Prospective studies
  • Retina
  • Sequence analysis, DNA
  • Ultrasonography, prenatal

ASJC Scopus subject areas

  • Epidemiology
  • Critical Care and Intensive Care Medicine
  • Nephrology
  • Transplantation


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