Tags

Type your tag names separated by a space and hit enter

Prospective Evaluation of Kidney Disease in Joubert Syndrome.
Clin J Am Soc Nephrol. 2017 Dec 07; 12(12):1962-1973.CJ

Abstract

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, and AHI1. 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.

Authors+Show Affiliations

Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.Due to the number of contributing authors, the affiliations are provided in the Supplemental Material. mgaygun@mail.nih.gov.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29146704

Citation

Fleming, Leah R., et al. "Prospective Evaluation of Kidney Disease in Joubert Syndrome." Clinical Journal of the American Society of Nephrology : CJASN, vol. 12, no. 12, 2017, pp. 1962-1973.
Fleming LR, Doherty DA, Parisi MA, et al. Prospective Evaluation of Kidney Disease in Joubert Syndrome. Clin J Am Soc Nephrol. 2017;12(12):1962-1973.
Fleming, L. R., Doherty, D. A., Parisi, M. A., Glass, I. A., Bryant, J., Fischer, R., Turkbey, B., Choyke, P., Daryanani, K., Vemulapalli, M., Mullikin, J. C., Malicdan, M. C., Vilboux, T., Sayer, J. A., Gahl, W. A., & Gunay-Aygun, M. (2017). Prospective Evaluation of Kidney Disease in Joubert Syndrome. Clinical Journal of the American Society of Nephrology : CJASN, 12(12), 1962-1973. https://doi.org/10.2215/CJN.05660517
Fleming LR, et al. Prospective Evaluation of Kidney Disease in Joubert Syndrome. Clin J Am Soc Nephrol. 2017 Dec 7;12(12):1962-1973. PubMed PMID: 29146704.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prospective Evaluation of Kidney Disease in Joubert Syndrome. AU - Fleming,Leah R, AU - Doherty,Daniel A, AU - Parisi,Melissa A, AU - Glass,Ian A, AU - Bryant,Joy, AU - Fischer,Roxanne, AU - Turkbey,Baris, AU - Choyke,Peter, AU - Daryanani,Kailash, AU - Vemulapalli,Meghana, AU - Mullikin,James C, AU - Malicdan,May Christine, AU - Vilboux,Thierry, AU - Sayer,John A, AU - Gahl,William A, AU - Gunay-Aygun,Meral, Y1 - 2017/11/16/ PY - 2017/05/26/received PY - 2017/09/18/accepted PY - 2017/11/18/pubmed PY - 2018/7/28/medline PY - 2017/11/18/entrez KW - Abnormalities, Multiple KW - Cerebellum KW - Ciliopathies KW - Eye Abnormalities KW - Genetic Association Studies KW - Joubert syndrome 1 KW - Kidney Diseases, Cystic KW - Kidney Failure, Chronic KW - Multicystic Dysplastic Kidney KW - Mutation KW - Phenotype KW - Polycystic Kidney, Autosomal Recessive KW - Pregnancy KW - Prospective Studies KW - Retina KW - Sequence Analysis, DNA KW - Ultrasonography, Prenatal KW - ciliopathy KW - cystic kidney KW - genetic renal disease KW - hypertension KW - kidney KW - nephronophthisis KW - polycystic kidney disease SP - 1962 EP - 1973 JF - Clinical journal of the American Society of Nephrology : CJASN JO - Clin J Am Soc Nephrol VL - 12 IS - 12 N2 - 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, and AHI1. 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. SN - 1555-905X UR - https://www.unboundmedicine.com/medline/citation/29146704/Prospective_Evaluation_of_Kidney_Disease_in_Joubert_Syndrome_ L2 - http://cjasn.asnjournals.org/cgi/pmidlookup?view=long&pmid=29146704 DB - PRIME DP - Unbound Medicine ER -